Article

[6]Gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Gingerol (Zingiber officinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. The oleoresin from rhizomes of ginger contains [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs which are pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, antihepatotoxic and cardiotonic effects. However, the effects of [6]-gingerol on metastatic processes in breast cancer cells are not currently well known. Therefore, in this study, we examined the effects of [6]-gingerol on adhesion, invasion, motility, activity and the amount of MMP-2 or -9 in the MDA-MB-231 human breast cancer cell line. We cultured MDA-MB-231 cells in the presence of various concentrations of [6]-gingerol (0, 2.5, 5 and 10 microM). [6]-Gingerol had no effect on cell adhesion up to 5 microM, but resulted in a 16% reduction at 10 microM. Treatment of MDA-MB-231 cells with increasing concentrations of [6]-gingerol led to a concentration-dependent decrease in cell migration and motility. The activities of MMP-2 or MMP-9 in MDA-MB-231 cells were decreased by treatment with [6]-gingerol and occurred in a dose-dependent manner. The amount of MMP-2 protein was decreased in a dose-dependent manner, although there was no change in the MMP-9 protein levels following treatment with [6]-gingerol. MMP-2 and MMP-9 mRNA expression were decreased by [6]-gingerol treatment. In conclusion, we have shown that [6]-gingerol inhibits cell adhesion, invasion, motility and activities of MMP-2 and MMP-9 in MDA-MB-231 human breast cancer cell lines.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... One research has shown that ginger components such as 6-and 10-gingerols have a beneficial role in the treatment of cervical cancer (Zhang et al., 2017). 6-gingerol has inhibited cell proliferation, induced apoptosis, and blocked G1 cell-cycle arrest in human colorectal cancer cells (Lee et al., 2008). In addition, it can induce apoptosis in human colorectal carcinoma cells through the activation of caspases (cysteine-aspartic proteases, cysteine aspartate, or cysteine-dependent aspartate-directed proteases) and the production of reactive oxygen species (Lee et al., 2008). ...
... 6-gingerol has inhibited cell proliferation, induced apoptosis, and blocked G1 cell-cycle arrest in human colorectal cancer cells (Lee et al., 2008). In addition, it can induce apoptosis in human colorectal carcinoma cells through the activation of caspases (cysteine-aspartic proteases, cysteine aspartate, or cysteine-dependent aspartate-directed proteases) and the production of reactive oxygen species (Lee et al., 2008). Several studies have shown that gingerol modulates a variety of cell signaling pathways linked to cancer, including nuclear factors (NF-κB), signal transducer and activator of transcription 3 (STAT3), activator protein-1 (AP-1), βcatenin, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), mitogen-activated protein kinases (MAPK), and pro-inflammatory mediators such as tumor necrosis factor (TNFα) and cyclooxygenase-2 (COX-2) (Jemal et al., 2009;Ling et al., 2010). ...
... Here are six articles that studied molecular biomarkers (Akimoto et al., 2015;Choudhury et al., 2010;Lee et al., 2008;Miyoshi et al., 2003;Saha et al., 2014), that the molecular factors of Bax and Bcl2 studied widely. Studies showed that Bax is increased and induced the opening of the mitochondrial voltage-dependent anion channel, so the death of the cell is guaranteed (Mignard et al., 2014). ...
Article
Full-text available
Ginger and its derivatives have been shown to be effective in the prevention and treatment of cancer. We undertook a systematic review to answer the question of whether ginger has a role in modifying the biomarkers of cancer in cell culture conditions and on colorectal cancer in randomized clinical trials. We performed a comprehensive search of the literature from Scopus, Embase, Web of Science, PubMed, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. At first, all 12 papers studied the effect of ginger or its derivatives on cell culture conditions. The results of cell culture studies show that ginger has a powerful role in inducing apoptosis. In the second part, five studies of clinical trials were analyzed. By analyzing antitumor markers of clinical trials, ginger increased some anticancer markers but performed poorly in inducing some anticancer markers. This systematic review showed that the consumption of ginger extract has the potential to prevent and treat colorectal cancer but this ability is weak. This systematic review showed that the consumption of ginger extract has the potential to prevent and treatment of colorectal cancer but this ability is weak.
... Ginger contains [6]-gingerol ( [6]-GIN), [6]-shogaol, [6]-paradol, and zingerones [10]. Among these components, [6]-GIN (1-[49-hydroxy-39-methoxyphenyl]-5-hydroxy-3-deca none) has been known to exhibit anticancer efficacy in various cancer cell lines [11][12][13][14][15]. ...
... Among these, [6]-GIN is the main active polyphenol of ginger and has been reported to exhibit antioxidant, anti-inflammatory, anticancer, neuroprotective, anti-obesity, and anti-hepatic steatosis effects [26][27][28][29][30][31][32]. It is also known to have anticancer effects on various cancer cells [11][12][13][14][15][33][34][35]. [6]-GIN has been shown to cause apoptosis in the cervical cancer cell line HeLa by activating the caspase-3-dependent pathway [11]. ...
... [6]-GIN has been shown to cause apoptosis in the cervical cancer cell line HeLa by activating the caspase-3-dependent pathway [11]. In previous studies, it inhibited the metastasis of the breast cancer cell line MDA-MB-231 and caused the apoptosis of the prostate cancer cell line LNCaP [12,13]. [6]-GIN also inhibits the growth of several types of murine tumors such as melanomas, renal cell carcinomas, and colon carcinomas [14,15]. ...
Article
Full-text available
The anti-cancer effects of [6]-gingerol ([6]-GIN), the main active polyphenol of ginger (Zingiber officinale), were investigated in the human bladder cancer cell line 5637. [6]-GIN inhibited cell proliferation, increased sub‑G1 phase ratios, and depolarized mitochondrial membrane potential. [6]-GIN-induced cell death was associated with the downregulation of B‑cell lymphoma 2 (BCL‑2) and survivin and the upregulation of Bcl‑2‑associated X protein (Bax). [6]-GIN activated caspase‑3 and caspase-9 and regulated the activation of mitogen-activated protein kinases (MAPKs). Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN‑induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment.
... The expression of Midkine is abnormally upregulated in various human cancers, especially in liver, lung and breast cancer [54]. Considering that many studies have reported an anti-cancer effect of 6-gingerol on various cancers [19,21,55,56], whether the similar mechanism of 6-gingerol is present in these aforementioned disease model warrants further research. cells caused by patulin [50] and lipopolysaccharide (LPS) [51]. ...
... The expression of Midkine is abnormally upregulated in various human cancers, especially in liver, lung and breast cancer [54]. Considering that many studies have reported an anti-cancer effect of 6-gingerol on various cancers [19,21,55,56], whether the similar mechanism of 6-gingerol is present in these aforementioned disease model warrants further research. 1-AP) were obtained from Proteintech (Rosemont, IL, USA). ...
Article
Full-text available
6-Gingerol, one of the major pharmacologically active ingredients extracted from ginger, has been reported experimentally to exert hepatic protection in non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism remains largely elusive. RNA sequencing indicated the significant involvement of the AMPK signaling pathway in 6-gingerol-induced alleviation of NAFLD in vivo. Given the significance of the LKB1/AMPK pathway in metabolic homeostasis, this study aims to investigate its role in 6-gingerol-induced mitigation on NAFLD. Our study showed that 6-gingerol ameliorated hepatic steatosis, inflammation and oxidative stress in vivo and in vitro. Further experiment validation suggested that 6-gingerol activated an LKB1/AMPK pathway cascade in vivo and in vitro. Co-immunoprecipitation analysis demonstrated that the 6-gingerol-elicited activation of an LKB1/AMPK pathway cascade was related to the enhanced stability of the LKB1/STRAD/MO25 complex. Furthermore, radicicol, an LKB1 destabilizer, inhibited the activating effect of 6-gingerol on an LKB1/AMPK pathway cascade via destabilizing LKB1/STRAD/MO25 complex stability in vitro, thus reversing the 6-gingerol-elicited ameliorative effect. In addition, molecular docking analysis further predicated the binding pockets of LKB1 necessary for binding with 6-gingerol. In conclusion, our results indicate that 6-gingerol plays an important role in regulating the stability of the LKB1/STRAD/MO25 complex and the activation of LKB1, which might weigh heavily in the 6-gingerol alleviation of NAFLD.
... Gingerol works by affecting the structure of lipid rafts in MDA-MB-231 IR cells and reducing the activity of key signaling pathways within the lipid rafts. [15][16][17] ...
Article
Full-text available
Cancer is a type of chronic disease which is the main cause of death in the world with 19.3 million new cases in 2020. Current cancer treatment includes surgery, chemotherapy, radiotherapy, hormone therapy, antiangiogenesis inhibitors, stem cell therapy, and others. Long-term cancer treatment can cause other health problems, so alternative anti-cancer therapy with the fewest side effects is needed. One natural ingredient that is known to prevent and act as anti-cancer therapy is Zingiber officinale. Zingiber officinale contains gingerol which functions as an anti-oxidant, anti-inflammatory, anti-bacterial, anti-cancer, anti-tumor and anti-mutagenic. The anticancer effects of gingerol are known to be effective in cancers of the liver, stomach, mouth, prostate, breast and ovaries. This literature aims to delve deeper into the role of gingerol as an anti-cancer compound. The strategy employed in the article search involved using electronic databases such as Google Scholar and PubMed. Keywords utilized included "cancer," "red ginger," "gingerol," "Zingiber officinale," and "anticancer." The articles selected were those published within the last 10 years. The study results indicate that gingerol is beneficial in oral, breast, lung, colorectal, cervical, and prostate cancers. The mechanism of action of gingerol involves pathways such as the PI3K/AKT, JAK/STAT, apoptosis, and ROS proliferation pathways. Gingerol is known to be effective as an anti-cancer agent and has the potential to become one of the alternative anti-cancer treatments.
... Kanser hastalıklarını tedavi etmede temel yöntemler kemoterapi, radyoterapi, cerrahi müdahale ve immünoterapidir (Ağan ve Kekeçoğlu, 2020;Ertürk, 2006 Hung et al., 2009;Qi et al., 2015;Chen et al., 2010), 6-gingerol (Jeong et al., 2009;Park et al., 2006;Lee et al., 2008;Radhakrishnan et al., 2014;Rastogi et al., 2015;Al-Abbasi et al., 2016), kuersetin (Vafadar et al., 2020;Gulati et al., 2006; Shafabakhsh and Asemi, 2019), p-kumarik asit (Jaganathan et al., 2013;Peng et al., 2015), kaemferol (Yoshida et al., 2008;Luo et al., 2011;Choi and Ahn, 2008) (Murakami et al., 2008). ...
Chapter
İlerleyen teknoloji, çevre kirliliğinin giderek artması ve hayat şartlarının daha da stresli bir hale gelmesi insanlarda sayısı yüzlerle ifade edilen çeşitli hastalıklara sebep olmaktadır. Bu hastalıkların en önemlilerinden biri de kanserdir. Kanser, genetik açıdan, doku ve hücre biyolojisi, tedaviye yanıt vermesi açısından göz korkutucu bir hastalıktır (Hanahan, 2022). Dünyada her yıl binlerce insan birçok çeşidi olan bu hastalığa yakalanmaktadır. Maalesef tam bir tedavi yöntemi henüz bulunamadığından binlerce insan kanserden ve kanserin sebep olduğu diğer hastalıklardan hayatını kaybetmektedir. Dünyada ölüm sebebi dikkate alındığında kanser ikinci sırada gelmektedir (Akeren ve Hintistan, 2021). Hastalığın tedavisi için kullanılan ilaçlar, sentetik olduklarından dolayı birçok yan etkiye sahiptirler (Ağan ve Kekeçoğlu, 2020). Ayrıca oldukça maliyetlidirler. Sentetik ilaçların bu olumsuzluklarından dolayı alternatif tedavi yöntemlerine yönelme olmuştur (Karakoç, 2020). Doğal kaynaklardan 6-shogaol (Ray et al., 2015; Bawadood et al., 2020), kuersetin (Vafadar et al., 2020), 6-gingerol (Rastogi et al., 2015), p-kumarik asit (Peng et al., 2015), kaemferol (Luo et al., 2011) gibi doğal bileşikler elde edip bunların kanser tedavilerinde kullanımını sağlamak amacıyla araştırmalar yapılmaktadır. Bu alan giderek artan ilgi gören bir araştırma sahası durumundadır (Akdulum, 2011). Doğal bileşikler içerisinde fenolik bileşiklerin antioksidan, antiproliferatif, apoptotoik, antimikrobiyal, antidiyabetik, antiinflamatuar, antipatojenik etkilerinin olduğu birçok çalışma ile ortaya konulmuştur. Örneğin oleropinin antiproliferatif, antimetastatik ve proapoptotik mekanizma yolları ile kanser tedavisinde kemoterapi ilaçları ile beraber kullanıldığında etkili olduğu bulunmuş ve oleropin sayesinde kemoterapi ilaçlarının daha düşük dozlarda kullanılarak tedavilerin yapılabileceği belirtilmiştir (Sherif and Al-Gayyar, 2018). 6-Gingerol’ün p53’e bağlı iç kaynaklı apoptozu indüklediği ve hormona bağlı meme kanseri hücrelerine karşı aday ilaç olabileceği belirtilmiştir (Sp et al., 2021). 6-Shogaol’ün tek başına veya kemoterapötik ajanlarla beraber kolorektal kanser hücreleri üzerinde sitotoksik etki gösterdiği ve geleneksel kemoterapiden daha güçlü olduğu bildirilmiştir (Woźniak et al., 2020). Bunlara benzer çalışmalara bakıldığında olumlu anlamda birçok rapor verildiği için fenolik bileşiklerin bu özelliklerinden tedavi süreçlerinde yararlanmak sağlık açısından oldukça önemlidir.
... Numerous studies in recent years have explored the preventive effects of ginger on cancer cell proliferation under in vitro and in vivo conditions (14)(15)(16)(17)(18). Regarding ginger's impact on breast cancer, studies have demonstrated that [6]-gingerol inhibits metastasis of MDA-MB-231 human breast cancer cells, resulting in a 16% reduction in invasion and motility at a ginger extract concentration of 10µM (19). Moreover, using chitosan-coated nanostructured lipid carriers (CS-NLCs) for (6)-gingerol delivery to MCF-7 breast cancer cells has demonstrated significant cytotoxic activity against MCF-7 cancer cells, while showing minimal impact on human umbilical vein endothelial (HUVEC) normal cell line (20). ...
Article
Full-text available
Introduction and Aim: Breast cancer ranks among the leading causes of death in women worldwide. Ginger has shown potential efficacy against certain cancer types, surpassing conventional therapies such as chemotherapy and radiation. However, its molecular mechanisms remain less understood. Materials and Methods: In this study, MCF-7 cancer cells were cultured and treated with various concentrations of aqueous ginger extract (20, 30, 45, 65 μg/mL) for 12, 48, and 72 hours. The effects were assessed through gene expression analysis and cell vitality assays (MTT). Results: The cell vitality test revealed a direct correlation between cytotoxicity and extract concentration. Concentrations exceeding 30 μg/mL exhibited significant cell death (IC50 of 104.03 μg/mL). Gene expression analysis demonstrated an increase in Patched-1 and a decrease in Gli1 expression with rising extract concentrations. The maximum Patched-1 expression occurred at 65 μg/mL after 72 hours. Patched-1 (oncogene) and Gli1 (tumor suppressor) are pivotal genes in the hedgehog (Hh) signalling pathway associated with breast cancer. Conclusion: It appears that ginger compounds play a substantial role in regulating cancer progression by influencing key components of the hedgehog signalling pathway.
... Ginger (Zingiber officinale) is one of the most popular spices worldwide and is widely used in food, medicines, drinks and toiletries around the globe Ali, 2009;Shah and Seth, 2010). The important medicinal part of the ginger plant is its rhizome which contain active compounds that inhibits colon cancer and suppression of the transformation, hyperproliferation of cells, and inflammation that initiate and promote carcinogenesis, angiogenesis and metastasis (Lee et al., 2008). ...
... transformation, hyperproliferation of cells, and inflammation that initiate and promote carcinogenesis, angiogenesis and metastasis (Lee et al., 2008). ...
Article
Full-text available
Ginger (Zingiber officinale) is a well known and widely used herb, especially in Asia, which contains several interesting bioactive constituents and possesses health promoting properties. In this study, phytochemical content as well as antimicrobial properties of Nigerian and Indian ginger were assessed in an effort to compare and validate the medicinal potential of the plant. Aqueous, hydromethanolic and hydroethanolic extracts of Indian and Nigerian ginger were prepared by extraction process. Both varieties were found to contain high amount of secondary metabolites. The comparison, carried out between different extracts of the two varieties using t-test at p=0.05, have shown no any significant difference in terms of antimicrobial activity while none of the samples show any activity against a fungus spp: Candida spp. This study validated the medicinal potential of Zingiber officinale.
... The main ingredients of the spicy group are gingerol, zingeron, shogaol and zingerol [3][4][5][6] ... Ginger contains 1.0% to 3.0% volatile oils and a number of pungent compounds [7]. Ginger is one of the medicinal species commonly used to treat diseases such as rheumatism, sore throat, abdominal pain, indigestion, vomiting, hypertension, fever, infectious diseases... [8], with prominent cytotoxic activity on cancer cells, especially breast cancer [9], ovarian cancer [10], pancreatic cancer [11]. After heat treatment, gingerols can be transformed into corresponding shogaols [12]. ...
Article
Full-text available
Ginger (Zingiber officinale) and its components have unique therapeutic effects such as anti-cancer, antioxidant, free radical blockers, antibacterial, anti-inflammatory. Among the compounds of ginger, [6]-shogaol is a promising cancer preventive compound. The purpose of this paper was to present the extraction, development and validation by high performance liquid chromatography (HPLC) assay with photodiode-array detector (PDA) for [6]-shogaol in ginger root. Dried ginger Zingiber officinale (1 kg) is extracted with EtOH 90% 60˚C in 3 hours under condition of ultrasound wave, the ratio of material and solvent is 1:5 give a crude extract (170 g). Conducting column chromatography (CC) with crude extract in n-hexane - EtOAc (50:1) to EtOAc 100% collected 7 fractions. Fraction 3 was applied CC in different mixture of solvents to give [6]-shogaol (10.5 mg). The quantitative process was carried out using reverse phase column VDSpher PUR 100 C18 (25 cm × 4.6 mm, 5 µm), the mobile phase was acetonitrile - 0.1% H3PO4. The gradient elution was as follows: 0 min 10% B, 3.5 min 18% B, 4.5 min 35% B, 6 min 40% B, 10 min 20% B; flow rate 1.0 mL/min; run time in 10 minutes; injection volume 20 µL; column temperature 25℃; wavelength at 280 nm. This HPLC method allowed for the detection of [6]-shogaol in a short run time of 10 minutes. Quantitative results showed that the process had high specificity, achieved linearity with the linear regression equation y = 166129.76x + 22743.83 and correlation coefficient R2 = 0.9997, achieved the repeatability criterion with the RSD of the concentration = 1.99%, the recovery rate accuracy was 99.30% with RSD = 1.34%, limit of detection and limit of quantification were 0.41 μg/mL and 1.25 μg/mL, respectively.
... Jordanian zhourat is a potent stimulator of innate and acquired immunity. The high antiproliferative activity of ginger is consistent with those from previous studies that reported similar behavior of ginger [6]-gingerol against MDA-MB-231 human breast cancer cell lines, which inhibits cell adhesion, invasion and motility [10] . Cancer preventive properties of ginger is also explained by the presence of flavonoid and polyphenolic components especially quercetin [11] . ...
Article
Full-text available
In this study immunomodulatory and antitumor activity of five herbal drinks consumed in Jordan were evaluated. The antiproliferative activity was determined using MTT assay. The degree of apoptosis induction was detected by TUNEL colorimetric assay. ELISA was used to measure VEGF expression in tumor cells and levels of cytokines secreted by splenocytes. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay. The growth of breast cancer cell lines was inhibited by herbal drinks in dose dependent manner. Ginger and lemon verbena were the most potent, they target cancer cells through the induction of apoptosis and suppression of breast cancer angiogenesis. An increase in Th1 cytokines level and decrease inTh2 cytokine level were evident after lymphocytes stimulation by herbal drinks. The consumption of different herbal drinks provides variable health benefits. Ginger and lemon verbena herbal drinks exhibit anticancer activities. Jordanian zhourat is a potent stimulator of innate and acquired immunity.
... However, this process can also promote chronic cancer cell death by inhibiting inflammatory mediators like interleukin (IL)-4, IL-6, interferon (IFN)-γ, and transforming growth factor (TGF)-β [13,32]. Tumor cells secrete matrix metalloproteases (MMPs) and proteolytic enzymes, along with inflammatory cytokines, that degrade the extracellular matrix forming the cellular scaffold and modulate the intra-tumoral environment [33,34]. ...
Article
Full-text available
Korean mistletoe (Viscum album var. coloratum) has been traditionally used as a remedy for cancer, diabetes, and hypertension. This study investigated the immuno-modulatory effects of Korean mistletoe water extract, specifically on MDA-MB-231 cells, a highly metastatic breast cancer cell line, when co-cultured with THP-1 human macrophage cells. When compared to MDA-MB-231 cells cultured alone, the co-culture of MDA-MB-231/THP-1 cells treated with mistletoe extract showed a significant reduction in IL-6 secretion. Additionally, these co-cultures exhibited elevated levels of IL-4, TGF-β, and IFN-y. These results suggest that water extracts from mistletoe have the potential to induce mitochondria-targeted apoptosis in MDA-MB 231 cells stimulated by THP macrophages. Regarding apoptosis, in MDA-MB-231 cells co-cultured with THP-1 macrophages, mistletoe water extract treatment triggered a significant increase in Bax/Bcl-2 ratio, caspase-3 activation, and PARP inactivation. In addition, there was a significant increase in E-cadherin and a decrease in N-cadherin. Treatment of Korean mistletoe also led to significant reductions in both MMP-2 and -9. Furthermore, inhibition of cell migration in MDA-MB-231/THP-1 co-cultured cells was observed. In summary, this study highlights the potential of Korean mistletoe as a prospective drug for the treatment of triple-negative breast cancer, particularly through its ability to regulate human immunity.
... Therefore, DENV can alter vascular permeability through changes in the physiological balance between MMPs and TIMPs [92][93][94]. 6-Gingerol (6G) and 6-shagaol (the biologically active components of ginger) may be applicable in vitro models of several diseases by downregulating the expression of MMP-2 and MMP-9 while upregulating the TIMPs activity [95][96][97][98][99]. Subsequently, 6G reduced the severity of DENV infection by balancing the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in DENV-infected cells [100,101]. ...
Article
Herbal medicine has gained massive popularity among researchers worldwide. The leading causes of this rapid development are lower side effects, lower prices, and higher availability of plant extracts compared to synthetic drugs. Ginger (Zingiber officinale), from the Zingiberaceae family, is one of the most commonly used and popular plants utilized as a dietary spice, herbal medicine, and food preservative. Its biologically active components, such as shogaol, paradol, zingerone, and especially gingerol, can be highly effective for the treatment of several illnesses through various anti-inflammatory, anti-neoplastic, anti-emetic, anti-oxidant, antihyperlipidemic and anti-hyperglycaemic activities. Ginger can also be used as an antiviral agent. Numerous studies have been conducted to investigate the antiviral efficacy of ginger on several viruses; for instance, severe acute respiratory syndrome 2 (SARS-COV-2), influenza, dengue, hepatitis, herpes, Human Papilloma Virus (HPV), Human Immunodeficiency Virus (HIV), Epstein- Barr Virus (EBV), Chikungunya virus and so on. This review summarizes the efficacy of ginger in preventing or treating several viral diseases and its mechanism of action, emphasizing coronavirus disease 2019 (COVID-19) due to the current high burden of disease worldwide.
... The major chemical components of ginger rhizomes are gingerols, shogaols, and zingerones. Among these components, 6-gingerol is the main pungent component and is believed to exert a variety of remarkable pharmacological and physiological activities, including antiinflammatory [4][5][6][7], anti-diabetic [8,9], anti-hepatic steatosis [10], anti-oxidant [6,11], and anti-cancer [12,13] effects. 6-Gingerols have also been reported to have anti-obesity properties, in 3T3-L1 preadipocytes, 6-gingerol shows inhibitory adipocyte differentiation [14][15][16]. ...
Article
Full-text available
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum triglyceride, leptin and insulin levels, and HOMA-IR in HFD-fed mice. Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.
... Anti-cancer Effect Z. officinale exhibits anti-inflammatory and anti-tumorigenic effects due to its bio active molecules such as 6-gingerole, 6-shogaol, 6-paradol and zerumbone, as a result prevention or control from colorectal, gastric ovarian, liver, breast and prostate cancers is possible. [38][39][40][41][42][43][44][45] Z. officinale activates enzymes such as glutathione peroxidase, glutathione s transferase and glutathione reductase and suppress colon carcinogenesis. 46 Oral administration of Zerumbone effects in inhibition of multiplicity of colonic adenocarcinomas through suppression of colonic inflammation due to inhibition of proliferation, induction of apoptosis and suppression of NF-ĸB and heme oxygenase (HO)-1 expression. ...
Article
Ginger, the rhizome of Zingiber officinale, species of the ginger family (Zingiberaceae) has a long history of medicinal use for more than 2000 years as one of the most versatile medicinal plants having a wide spectrum of biological activity and a common condiment for various foods and beverages. Rhizome of Zingiber officinale (ginger) is extensively used in medicinal purpose. Ayurveda literatures highlight administration of ginger in both of communicable and non-communicable diseases. Recent advances in analytical chemistry, cytology and microbiology recommend application of ginger in various disease conditions as well as recommendations in Ayurveda literature. The medicinal properties of ginger are due to the presence of gingerol and paradol, shogaols, etc… Currently, there is a renewed interest in ginger. Therefore, in the current study we aimed to describe and delineate on medicinal activites of Z. officinale including antiviral, anti-inflammatory, antioxidant, cardiovascular, gastrointestinal, and neuroprotective activities.
... For example, 6-gingerol was found to protect HUVEC cells against hydrogen peroxide-induced apoptosis via the induction of autophagy and by increasing the expression of Bcl-2. 84 Similarly, the anti-inflammatory 86 and anticancer 87,88 properties of 6-gingerol have also been reported. Then, 6-gingerol may be a potential anti-inflammatory and anticancer agent in snail mucus. ...
Article
This study reports the novel use of Achatina fulica (A. fulica) mucus as a potential therapeutic repair agent in osteoarthritis and cartilage tissue repair in vitro. Snail mucus was isolated, sterilized, and characterized using FTIR, XPS, rheology, and LC-MS/MS. The GAGs, sugar, phenol, and protein contents were estimated using standard assays. The LC-MS/MS identified 6-gingerol and some other small molecules. The effects of the sterilized mucus were studied on human chondrocytes using the C28/I2 cell as a model for the in vitro assays. The MTT assay indicates that mucus extracted from the pedal of A. fulica is biocompatible with the cells up to a concentration of 50 μg/mL. The mucus promoted cell migration and proliferation and completely closed the wound within 72 h, as indicated in the in vitro scratch assay. In addition, the snail mucus reduced apoptosis significantly (p < 0.05) in the treated cells by 74.6%. It preserved the cytoskeletal integrity of the C28/I2 cells, attributed mainly to GAGs and 6-gingerol content of the mucus. In conclusion, this present study suggests that GAGs and 6-gingerol conferred wound-healing and antiapoptotic properties on the mucus secretion from A. fulica and can be explored for therapeutic repair and cartilage tissue engineering.
... It is able to significantly decrease cell viability in a dose-dependent manner, particularly in osteosarcoma cells [101]. It sensitizes cell death induced by TRIAL (Tumor necrosis factor (TNF)-related apoptosis-inducing ligand) via apoptosis [102,103] and sensitizes the chemotherapy protocol with cyclophosphamide/adriamycin, preventing the initiation and progression of BC through inhibitory effects [104,105]. Despite the numerous biological properties of 6-gingerol, its low bioavailability is the main challenge that limits its application. ...
Article
Full-text available
Simple Summary Cancer is one of the most dangerous diseases in humans, and no permanent therapy has been developed yet. Breast cancer (BC) is one of the most common cancers in women. The purpose of this review was to clarify how natural products may play a role in the prevention, treatment and progression of BC. For all the compounds examined, in vitro and in vivo studies, as well as clinical studies on BC, are described. Abstract In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.
... Estudios previos con Zingiber officinale demostraron que esta especie exhibía varios efectos benéficos, entre los que destaca como anticancerígeno (9)(10)(11) , antiemético (12) , gastroprotector (13,14) , antibacteriano (15) , antiagregante plaquetario (16) , antihipertensivo (17) , entre otros importantes efectos. ...
Article
Full-text available
Objetivo. Evaluar la capacidad antioxidante in vitro del liofilizado de la pulpa y cáscara del rizoma de Zingiber officinale Roscoe (jengibre) mediante los ensayos DPPH, FRAP y TBARS. Materiales y métodos. Se separó la pulpa y la cáscara de los rizomas de Z. officinale, se preparó un macerado con solución hidroalcohólica (70:30 EtOH:H2 O), y luego de rotaevaporar, se liofilizó. La capacidad antioxidante de los liofilizados se evaluó según porcentaje de inhibición del radical DPPH y el poder antioxidante de reducción férrica (FRAP), así como la capacidad de inhibir la peroxidación lipídica in vitro mediante el ensayo TBARS. Resultados. Los extractos liofilizados de la pulpa y cáscara evidenciaron moderada capacidad antioxidante, siendo similar según porcentaje de inhibición del radical DPPH (46,5 y 45,6% respectivamente). Sin embargo, mediante el ensayo FRAP la cáscara presentó una capacidad antioxidante de 31,09 µg/mL expresados como equivalentes de trolox (ET) en comparación a la pulpa (22,96 µg ET/mL). Además, solo el liofilizado de cáscara del rizoma de Z. officinale a bajas concentraciones (0,1, 0,2 y 0,3 mg/mL) es capaz de reducir significativamente (p < 0,01) la peroxidación lipídica in vitro. Conclusión. La cáscara del rizoma de Z. officinale posee mayor capacidad antioxidante en comparación con la pulpa según los ensayos FRAP y TBARS; sin embargo, la inhibición de radicales DPPH fue la misma tanto en la cáscara como en la pulpa.
... Worldwide, ginger has been used for culinary and episodes [35] . Patients with BC who breathed ginger essential oil reported significantly lower acute nausea scores, but there was no discernible difference in the overall therapeutic effect compared to those who did not. ...
Article
Currently, one of the most challenging diseases to tis breast cancer. Hormone therapy, surgery, chemotherapy, and radiation have all been used to treat breast cancer for a long time, but they are become eating less and less successful due to serious side effects and rising drug resistance. Numerous dietary foods have been linked to altered cancer genesis and progression pathways, decreased aggressiveness, and growth inhibition of malignant cells. These dietary foods may be advantageous compared to produce medications since they exhibit lower toxicity and negative effects in various investigations. The promises made by dietary foods for breast cancer treatment by focusing on several pathophysiological cascades involved in the onset and progression of breast cancer and their capacity to simultaneously stop metastatic and growth progression. Some of the extensively researched numerous dietary foods that specifically target certain breast cancer pathways and express any of the three attributes are mentioned in article
... Worldwide, ginger has been used for culinary and episodes [35] . Patients with BC who breathed ginger essential oil reported significantly lower acute nausea scores, but there was no discernible difference in the overall therapeutic effect compared to those who did not. ...
Article
Currently, one of the most challenging diseases to tis breast cancer. Hormone therapy, surgery, chemotherapy, and radiation have all been used to treat breast cancer for a long time, but they are become eating less and less successful due to serious side effects and rising drug resistance. Numerous dietary foods have been linked to altered cancer genesis and progression pathways, decreased aggressiveness, and growth inhibition of malignant cells. These dietary foods may be advantageous compared to produce medications since they exhibit lower toxicity and negative effects in various investigations. The promises made by dietary foods for breast cancer treatment by focusing on several pathophysiological cascades involved in the onset and progression of breast cancer and their capacity to simultaneously stop metastatic and growth progression. Some of the extensively researched numerous dietary foods that specifically target certain breast cancer pathways and express any of the three attributes are mentioned in article.
... [66][67][68] Moreover, one study has reported that 6-gingerol can reduce the activity and mRNA expression of MMP-9 but leaves its protein levels unchanged. 71 Therefore, supplementation with higher doses of ginger and assessment of MMP-9 activity and mRNA expression are recommended for future trials. In addition, the measurement of tissue inhibitor of metalloproteinase-1, a specific inhibitor of MMP-9, may help better interpret the findings. ...
Article
Introduction: Different lines of evidence have shown that ginger administration may be beneficial for patients with multiple sclerosis (MS). Therefore, we aimed to investigate the effect of ginger supplementation on disability, physical and psychological quality of life (QoL), body mass index (BMI), neurofilament light chain (NfL), interlukin-17 (IL-17), matrix metalloproteinase-9 (MMP-9), and neutrophil to lymphocyte ratio (NLR) in patients with relapsing-remitting MS. Methods: This was a 12-week double-blind parallel randomized placebo-controlled trial with a 3-week run-in period. The treatment (n = 26) and control (n = 26) groups received 500 mg ginger and placebo (corn) supplements 3 times daily, respectively. Disability was evaluated using the Expanded Disability Status Scale (EDSS). QoL was rated by the Multiple Sclerosis Impact Scale (MSIS-29). BMI was calculated via dividing weight by height squared. Serum levels of NfL, IL-17, and MMP-9 were measured using the enzyme-linked immunosorbent assay. NLR was determined by the Sysmex XP-300™ automated hematology analyzer. All outcomes were assessed before and after the intervention and analyzed using the intention-to-treat principle. Results: In comparison with placebo, ginger supplementation caused a significant reduction in EDSS (-0.54 ± 0.58 vs. 0.08 ± 0.23, P < 0.001), MSIS-29 physical scale (-8.15 ± 15.75 vs. 4.23 ± 8.46, P = 0.001), MSIS-29 psychological scale (-15.71 ± 19.59 vs. 6.68 ± 10.41, P < 0.001), NfL (-0.14 ± 0.97 vs. 0.38 ± 1.06 ng/mL, P = 0.049), IL-17 (-3.34 ± 4.06 vs. 1.77 ± 6.51 ng/L, P = 0.003), and NLR (-0.09 ± 0.53 vs. 0.53 ± 1.90, P = 0.038). Nevertheless, the differences in BMI and MMP-9 were not significant between the groups. Conclusion: Ginger supplementation may be an effective adjuvant therapy for patients with relapsing-remitting MS.
... It also demonstrates a variety of biological functions, including antibreast cancer activity, antitubercular activity, analgesic, antiinflammatory, antihypertensive, CNS activity, antioxidant, antiviral, antidiabetic [25] , antimicrobial [26] , immunosuppressive activities [27] .It also demonstrates biological processes such as COX-2 inhibitors [28] , anti-hypnotics [29] , anti-allergic [30] , and HIV-1 inhibitors [31] .The significant inhibitory activity of triazolone scaffold against anticancer has been thoroughly investigated by numerous research organizations [32][33][34] . A few of the pyrazolothiazolone compounds have been created [35][36] , and they have activity against the dengue virus [37] as well as being anti-proliferative [38] , anticonvulsant [39] , antimicrobial and antiinflammatory [40] , antiviral [41] , anti-HIV-1 NNRT inhibitors [42] , anticancer [43][44] .In an effort to aid in the drive against breast cancer, we screened a number of synthetic compounds incorporating fused heterocycles for possible biological activity. ...
Article
Full-text available
Mainstream cancer research has continued to place a significant emphasis on the development of new and effective therapeutic candidates to tackle rising treatment resistance and off-target toxicities. Here, a series of novel 3-(substitutedphenyl)-2-(4-(substitutedphenyl)thiazol-2-yl)-2Hpyrazolo[3,4-d]thiazol-5(6H)-one derivatives were synthesized and characterized. The ability of the synthesized compounds to reduce the survival of the human breast cancer cell line MDA-MB 231 was evaluated. When compared to the reference chemical, 5-fluorouracil, 3-(4-chlorophenyl)-2-(4- (4-chlorophenyl)thiazol-2-yl)-2H-pyrazolo[3,4d]thiazol-5(6H)-oneand 3-(4-nitrophenyl)-2-(4-(4-nitrophenyl)thiazol-2-yl)-2H-pyrazolo[3,4d]thiazol5(6H)-oneshowed the highest inhibitory activity (IC50:550 0.78 M and 504 0.89, respectively) on the viability of MDA-MB 231 cells. A molecular docking study has been carried out to discover more potent drugs.
... This pharmacologically active compound possesses substantial antimutagenic and anticarcinogenic activities [14]. An abundance of mounting evidence supports that 6-gingerol is potentially effective in suppressing the transformation, hyperproliferation and inflammatory changes that promote carcinogenesis, angiogenesis and metastasis [15][16][17]. Despite the awareness of 6-gingerol therapeutic potential against several cancers, the exact molecular mechanism underlying the anticancer role of 6-gingerol is not fully clear. ...
Article
Full-text available
A polyphenolic component of ginger, 6-gingerol, is widely reported to possess antioxidant, anti-inflammatory and anticancer activities. In the current study, it was aimed to investigate the anticancer effects of 6-gingerol (6-Gin) on azoxymethane (AOM)-induced colon cancer in rats. The results reveal that 6-Gin treatment significantly improves the antioxidant status disturbed by AOM intoxication. The 6-Gin treatment animal group showed enhanced activity of catalase (CAT) (46.6 ± 6.4 vs. 23.3 ± 4.3 U/mg protein), superoxide dismutase (SOD) (81.3 ± 7.6 vs. 60.4 ± 3.5 U/mg protein) and glutathione-S-transferase (GST) (90.3 ± 9.4 vs 53.8 ± 10 mU/mg protein) (p < 0.05) as compared to the disease control group. Furthermore, the results reveal that AOM significantly enhances the inflammatory response and 6-gingerol potentially attenuates this response, estimated by markers, such as tumor necrosis factor-α (TNF-α) (1346 ± 67 vs. 1023 ± 58 pg/g), C-reactive protein (CRP) (1.12 ± 0.08 vs. 0.92 ± 0.7 ng/mL) and interleukin-6 (IL-6) (945 ± 67 vs. 653 ± 33 pg/g). In addition, the lipid peroxidation estimated in terms of malondialdehyde (MDA) provoked by AOM exposure is significantly reduced by 6-gingerol treatment (167 ± 7.5 vs. 128.3 nmol/g). Furthermore, 6-gingerol significantly maintains the colon tissue architecture disturbed by the AOM treatment. Loss of tumor suppressor protein, phosphatase and tensin homolog (PTEN) expression was noticed in the AOM treated group, whereas in the animals treated with 6-gingerol, the positivity of PTEN expression was high. In conclusion, the current findings advocate the health-promoting effects of 6-gingerol on colon cancer, which might be due to its antioxidant and anti-inflammatory potential.
... Therefore, inhibition of VEGF and FGF is an important step in the prevention of tumor development/management [19] . The active ingredient 6-gingerol has considerable role in the suppression of neoplastic transformation, hyper proliferation, and inflammatory processes that involve in various steps of carcinogenesis, angiogenesis and metastasis [20] . Several studies have shown that ginger has promising effect for liver cancer, breast cancer, prostate cancer and colorectal carcinomas through its diverse pharmaceutical mechanisms [21] . ...
... The plates were then washed thoroughly with water and dried. The cells were visualized under the microscope for the migration of cells across the wound [59,61,62]. Doxorubicin was used as a positive control and the vehicle as a negative control. ...
Article
Full-text available
c-Met is involved in cellular processes that lead to the development and progression of cancer. A series of 2, 4-dichlorophenoxyacetamide-chalcones were synthesized and evaluated for their antiproliferative activities against MCF-7, HT-29, and A549 cancer cell lines. Several compounds showed moderate-to-good antiproliferative activity against MCF-7 and A549 cell lines. Many compounds were inactive against the HT-29 cell line. Some selected compounds were tested against c-Met kinase using the ADP GloTM assay and were found to possess IC50 < 10 µM indicating good activity. Compound 6f was identified as a promising compound and evaluated further for its antiproliferative and antimigratory properties on MCF-7 and A549 cell lines using colony formation and wound healing assays, respectively. Compound 6f had long-term antiproliferative effects and exerted antimigratory activity on both cell lines. Compound 6f had better potential at inhibiting growth and migration in MCF-7 cells. Molecular docking studies indicated that these compounds bind to Met1160 from the hinge region. Furthermore, molecular dynamics simulation studies for compound 6f confirmed this finding. Docking-based selectivity studies showed that these compounds were more selective for c-Met kinase. Graphical abstract
... Phytochemicals that display chemosensitization potential include ursolic acid (pentacyclic terpene) [71], bentulinic acid (pentacyclic triterpene) [72], rutin (quercetin glycoside) [73], noscapine (benzylisoquinoline alkaloid) [74], resveratrol (stilbene phenol) [75], curcumin (diarylheptanoid phenol) [76], and genistein (isoflavone) [77] (Table 2). • Efficacy to induce cell death in multiple breast cancer cell-lines [82] • Inhibition of breast cancer proliferation, metastases, and angiogenesis and promotion of senescence and apoptosis [83] Mitochondrial respiratory uncoupling [84] Increased respiration, decreased ∆Ψm, inhibited electron transfer at high concentrations [85] Rapid calcium influx into the mitochondria and sustained decrease in ∆Ψm [86] • Efficacy to induce apoptosis and inhibit metastasis [105] In vitro • Efficacy to induce apoptosis [106,107] and induce metastasis [108] Modulated BcL-2 protein, cytochrome c release, increased caspase signaling [106] Permeabilization of OMM and cytochrome c release [107] ...
Article
Full-text available
Breast cancer is a common and deadly disease that causes tremendous physical, emotional, and financial burden on patients and society. Early-stage breast cancer and less aggressive subtypes have promising prognosis for patients, but in aggressive subtypes, and as cancers progress, treatment options and responses diminish, dramatically decreasing survival. Plants are nutritionally rich and biologically diverse organisms containing thousands of metabolites, some of which have chemopreventive, therapeutic, and sensitizing properties, providing a rich source for drug discovery. In this study we review the current landscape of breast cancer with a central focus on the potential role of phytochemicals for treatment, management, and disease prevention. We discuss the relevance of phytochemical targeting of mitochondria for improved anti-breast cancer efficacy. We highlight current applications of phytochemicals and derivative structures that display anti-cancer properties and modulate cancer mitochondria, while describing future applicability and identifying areas of promise.
... Ray et al. observed that 6-shogaol, a phenol present in ginger, induced autophagic cell death in breast cancer cells along with the modulation of the Notch signaling pathway [143]. Lee et al. found that gingerol, another phenolic compound in ginger, inhibited the metastasis of MDA-MB-231 human breast cancer cells [154]. These findings were corroborated by Martin et al. with similar observation in vivo [155]. ...
Article
Full-text available
In an attempt to find a potential cure for cancer, scientists have been probing the efficacy of the food we eat and its bioactive components. Over the decades, there has been an exponentially increasing trend of research correlating food and cancer. This review explains the molecular mechanisms by which bioactive food components exhibit anticancer effects in several cancer models. These bioactive compounds are mainly plant based or microbiome based. While plants remain the primary source of these phytochemicals, little is known about probiotics, i.e., microbiome sources, and their relationships with cancer. Thus, the molecular mechanisms underlying the anticancer effect of probiotics are discussed in this review. The principal mode of cell death for most food bioactives is found to be apoptosis. Principal oncogenic signaling axes such as Akt/PI3K, JAK/STAT, and NF-κB seem to be modulated due to these bioactives along with certain novel targets that provide a platform for further oncogenic research. It has been observed that probiotics have an immunomodulatory effect leading to their chemopreventive actions. Various foods exhibit better efficacy as complete extracts than their individual phytochemicals, indicating an orchestrated effect of the food components. Combining bioactive agents with available chemotherapies helps synergize the anticancer action of both to overcome drug resistance. Novel techniques to deliver bioactive agents enhance their therapeutic response. Such combinations and novel approaches are also discussed in this review. Notably, most of the food components that have been studied for cancer have shown their efficacy in vivo. This bolsters the claims of these studies and, thus, provides us with hope of discovering anticancer agents in the food that we eat.
... Gingerols were discovered to inhibit breast cancer cell proliferation and metastasis. By inhibiting cyclin-dependent kinases and cyclins, 10-gingerol inhibited MDA-MB-231 proliferation, resulting in a G1 phase arrest [42]. Moreover, 10-gingerol also inhibited cancer cell invasion by inhibiting the activation of Akt and p38 (MAPK) [43]. ...
Article
Full-text available
Cancer is one of the leading causes of death in the world, with breast cancer being the most prevalent cancer. Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious side effects of chemotherapy. Because the current CINV treatment option has several flaws, alternative treatment options are required. Ginger has traditionally been used to treat nausea and vomiting, and it also has anticancer properties in breast cancer cells. Based on these findings, researchers investigated whether using ginger to treat CINV in breast cancer patients is both effective and safe. We searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang from inception to June 2022. Outcomes included Rhodes Index Scores of Nausea, Vomiting, and Retching, severity and frequency of CINV. Five RCTs were included. We pooled all included data and performed subgroup analysis by types of CINV. Overall, authors found that ginger was associated with a reduction in CINV. Subgroup and sensitivity analysis revealed that managing severity of acute CINV in breast cancer patients with ginger was efficient. In terms of managing delayed CINV in breast cancer patients, ginger was also statistically significant. The authors concluded that ginger may be helpful in lowering both acute and delayed CINV in breast cancer patients. Since there were no serious side effects, ginger is thought to be safe.
... In vitro study on gastrointestinal cancer treated with [6]-gingerol showed a high increase of caspase-3/7 activation and down-regulation of cytosolic inhibitor of apoptosis (cIAP)-1 (Prasad & Tyagi, 2015). Other studies on glioblastoma showed the role of [6]-gingerol in increasing death receptors, apoptotic proteins such as Bax, as well as downregulating anti-apoptotic proteins like Survivin and Bcl-2 (Lee, et al., 2008). In liver cancer, there was a report for down-regulating NF-κB in the animal model, while in the HepG2 cell line, cathepsin D was detected followed by an increase in ROS production ( Yang et al., 2012). ...
Chapter
Full-text available
Carcinogenesis or tumourigenesis is a multistep process involving dysregulation in the basic cell functioning which is primarily induced by carcinogens owning to the initiation and development of cancer. Environmental exposure, lifestyle choices, infectious agents and inherited mutations are the major causative factors of cancer. Cancer is a major health burden that is diagnosed with 5,85,000 deaths and 1.6 million new cancer cases in the United States in 2014. For the past few decades, there was significant improvement in the treatment of cancer with more effective drugs but identified with unwanted side effects and poor prognosis. However, lack of success with the targeted therapies has led to the adoption of an alternative approach which is safe and avoids the expensive treatment options. Extensive research and advancement in the field of molecular biology has identified the various chemopreventive agents which provide a huge benefit to healthcare providers and thereby halt and prevent the incidence of cancer. Cancer chemoprevention is the use of synthetic, natural and biological agents to reverse, delay, inhibit and prevent the inception and progression of carcinogenesis. Numerous evidences have revealed that the phytochemicals derived from natural products are considered more promising due to their higher efficacy in reducing the risk of acquiring cancer. Cancer chemopreventive agents are further divided into various categories according to their effects on different carcinogenesis stages like the compounds which influence the initiation of cancer are blocking agents and the ones that effect the promotion and progression are suppressing agents. Unravelling the Role of Chemopreventive Agents as Modulators of Carcinogenesis C H A P T E R1 0 Unravelling the Role of Chemopreventive Agents as Modulators... 217 These chemopreventive agents are mainly of natural origin and thereby assumed to be safer than the prescribed drugs. Phytochemicals derived from fruits and vegetables, including ellagic acid, genistein, diallyl sulfide, allicin, 6-gingerol, S-allyl cysteine, capsaicin, lycopene, curcumin, ursolic acid, anethol, silymarin, and eugenol are referred to as chemopreventive agents. As these agents have been shown to inhibit growth factor of signalling pathways, suppress the proliferation of cancer cells, inhibit NF-kappa B, JAK-STAT and AP-1 activation pathways, induce apoptosis, inhibit cyclooxygenase-2, suppressing the expression of anti-apoptotic proteins, inhibit angiogenesis, therefore scientists are further investigating their potential for unraveling them as chemotherapeutic drugs. In the present chapter, we summarize the crucial role of definitive chemopreventive agents in modulating the different cellular processes and signaling pathways to overcome the incidence of cancer.
Article
Objectives: This study aims to analyze recent research on the pharmacological effects of Zingiber officinale.Methods: We searched for papers from databases such as ScienceON, RISS, DBPia, and NaNet. The papers were classified according to pharmacological effects, and the selected studies were analyzed.Results: Six studies were finally included in the study. 1. Four studies mainly focused on the effects of anti-inflammation using in vitro or in vivo experiments. 2. Two studies mainly focused on the effects of antioxidants using in vitro experiments. 3. Other pharmacological effects, including improvement of gastrointestinal function, inhibition of body temperature reduction, and anti-aging, were investigated using in vitro or in vivo studies.Conclusion: This study shows that Z. officinale has several pharmacological effects, including anti-inflammation and antioxidant.
Article
The aetiology of breast cancer is complicated. In population health, breast cancer significantly impacts the most typical invasive malignancy and the second most typical death source for women. The most crucial point for the best prognosis is identifying early-stage cancer cells. The conventional diagnostics test for breast cancer includes a physical examination, biopsy (Fine-needle aspiration biopsy, core needle biopsy, Surgical biopsy) and several imaging techniques like mammography (digital mammography, computer-aided detection and breast tomosynthesis), MRI (Magnetic Resonance Imaging). Several drugs are approved by Food and Drug Administration for breast cancer, among them, some are approved to prevent breast cancer; some are used to treat breast cancer and some drugs are used in combination mode. Clinical investigation reports revealed that breast cancer mortality decreased in association with smaller breast volume and hence to meet the goal exercise is highly recommended. Similarly, dietary fat has been proposed as one of the etiologic factors of breast cancer. Obesity, overweight and reduced physical activity, causes breast cancer. At an early stage, cancer detection could increase breast cancer survival rates significantly in the long term. In the present review we have represented the breast cancer, its current statistics, molecular classification, different causes, disease prognosis, diagnostic strategies, and management in details in a lucid way.
Article
Unlabelled: Alzheimer's disease (AD) is a neurodegenerative disease that causes deterioration in intelligence and psychological activities. Yet, till today, no cure is available for AD. The marine environment is an important sink of bioactive compounds with neuroprotective potential with reduced adverse effects. Recently, we collected the red algae Laurencia snackeyi from Terumbu Island, Malaysia which is known to be rich in halogenated metabolites making it the most sought-after red algae for pharmaceutical studies. The red alga was identified based on basic morphological characteristics, microscopic observation and chemical data from literature. The purplish-brown algae was confirmed a new record. In Malaysia, this species is poorly documented in Peninsular Malaysia as compared to its eastern continent Borneo. Thus, this study intended to investigate the diversity of secondary metabolites present in the alga and its cholinesterase inhibiting potential for AD. The extract inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 14.45 ± 0.34 μg mL-1 and 39.59 ± 0.24 μg mL-1, respectively. Subsequently, we isolated the synderanes, palisadin A (1), aplysistatin (2) and 5-acetoxypalisadin B (3) that was not exhibit potential. Mass spectrometry analysis detected at total of 33 additional metabolites. The computational aided molecular docking using the AChE and BChE receptors on all metabolites shortlisted 5,8,11,14-eicosatetraynoic acid (31) and 15-hydroxy-1-[2-(hydroxymethyl)-1-piperidinyl]prost-13-ene-1,9-dione (42) with best inhibitory properties, respectively with the lowest optimal combination of S-score and RMSD values. This study shows the unexplored potential of marine natural resources, however, obtaining sufficient biomass for detailed investigation is an uphill task. Regardless, there is a lot of potential for future prospects with a wide range of marine natural resources to study and the incorporation of synthetic chemistry, in vivo studies in experimental design. Supplementary information: The online version contains supplementary material available at 10.1007/s13205-023-03725-6.
Article
Full-text available
Background As the characteristic functional component in ginger, gingerols possess several health-promoting properties. Long non-coding RNAs (lncRNAs) act as crucial regulators of diverse biological processes. However, lncRNAs in ginger are not yet identified so far, and their potential roles in gingerol biosynthesis are still unknown. In this study, metabolomic and transcriptomic analyses were performed in three main ginger cultivars (leshanhuangjiang, tonglingbaijiang, and yujiang 1 hao) in China to understand the potential roles of the specific lncRNAs in gingerol accumulation. Results A total of 744 metabolites were monitored by metabolomics analysis, which were divided into eleven categories. Among them, the largest group phenolic acid category contained 143 metabolites, including 21 gingerol derivatives. Of which, three gingerol analogs, [8]-shogaol, [10]-gingerol, and [12]-shogaol, accumulated significantly. Moreover, 16,346 lncRNAs, including 2,513, 1,225, and 2,884 differentially expressed (DE) lncRNA genes (DELs), were identified in all three comparisons by transcriptomic analysis. Gene ontology enrichment (GO) analysis showed that the DELs mainly enriched in the secondary metabolite biosynthetic process, response to plant hormones, and phenol-containing compound metabolic process. Correlation analysis revealed that the expression levels of 11 DE gingerol biosynthesis enzyme genes (GBEGs) and 190 transcription factor genes (TF genes), such as MYB1 , ERF100 , WRKY40 , etc. were strongly correlation coefficient with the contents of the three gingerol analogs. Furthermore, 7 and 111 upstream cis -acting lncRNAs, 1,200 and 2,225 upstream trans -acting lncRNAs corresponding to the GBEGs and TF genes were identified, respectively. Interestingly, 1,184 DELs might function as common upstream regulators to these GBEGs and TFs genes, such as LNC_008452 , LNC_006109 , LNC_004340, etc. Furthermore, protein–protein interaction networks (PPI) analysis indicated that three TF proteins, MYB4, MYB43, and WRKY70 might interact with four GBEG proteins (PAL1, PAL2, PAL3, and 4CL-4). Conclusion Based on these findings, we for the first time worldwide proposed a putative regulatory cascade of lncRNAs, TFs genes, and GBEGs involved in controlling of gingerol biosynthesis. These results not only provide novel insights into the lncRNAs involved in gingerol metabolism, but also lay a foundation for future in-depth studies of the related molecular mechanism.
Article
Gynecologic cancers can make up the bulk of cancers in both humans and animals. The stage of diagnosis and the type of tumor, its origin, and its spread are a few of the factors that influence how effectively a treatment modality works. Currently, radiotherapy, chemotherapy, and surgery are the major treatment options recommended for the eradication of malignancies. The use of several anti-carcinogenic drugs increases the chance of harmful side effects, and patients might not react to the treatments as expected. The significance of the relationship between inflammation and cancer has been underscored by recent research. As a result, it has been shown that a variety of phytochemicals with beneficial bioactive effects on inflammatory pathways have the potential to act as anti-carcinogenic medications for the treatment of gynecologic cancer. The current paper reviews the significance of inflammatory pathways in gynecologic malignancies and discusses the role of plants-derived secondary metabolites that are useful in the treatment of cancer.
Article
Full-text available
Breast cancer is the leading cause of death among women worldwide, and certain subtypes are highly aggressive and drug resistant. As oxidative stress is linked to the onset and progression of cancer, new alternative therapies, based on plant-derived compounds that activate signaling pathways involved in the maintenance of cellular redox homeostasis, have received increasing interest. Among the bioactive dietary compounds considered for cancer prevention and treatment are flavonoids, such as quercetin, carotenoids, such as lycopene, polyphenols, such as resveratrol and stilbenes, and isothiocyanates, such as sulforaphane. In healthy cells, these bioactive phytochemicals exhibit antioxidant, anti-apoptotic and anti-inflammatory properties through intracellular signaling pathways and epigenetic regulation. Short-chain fatty acids (SCFAs), produced by intestinal microbiota and obtained from the diet, also exhibit anti-inflammatory and anti-proliferative properties related to their redox signaling activity—and are thus key for cell homeostasis. There is evidence supporting an antioxidant role for SCFAs, mainly butyrate, as modulators of Nrf2-Keap1 signaling involving the inhibition of histone deacetylases (HDACs) and/or Nrf2 nuclear translocation. Incorporation of SCFAs in nutritional and pharmacological interventions changes the composition of the the intestinal microbiota, which has been shown to be relevant for cancer prevention and treatment. In this review, we focused on the antioxidant properties of SCFAs and their impact on cancer development and treatment, with special emphasis on breast cancer.
Article
Cardiovascular disease (CVD) is the leading cause of death globally, and coronary heart disease (CHD) is the most prominent one among the spectrum of CVD. Conventional CHD drugs pose an increased risk of pharmaceutical interactions. Moreover, the possibility of tainting or substituting other medications also raises concerns. Diet and lifestyle play an important role in preventing and treating heart disease, and certain spices and supplements can help reduce the risk of heart disease and treat it. Spices have been an important part of Indian culture from the dawn of time, valued for both their culinary and medicinal virtues. Indian spices and their bioactive phytoconstituents are reported to play an ameliorating role in treating CHD. Despite the fact that the majority of these spices have an effect on organic components associated with the cardiovascular system, data on their therapeutic effects is sparse. To make the most of the enormous potential of these spices, multidisciplinary research is the need of the hour to establish them as remedies for CVDs. We endeavour to document some ethnopharmacological studies aimed to establish the cellular and molecular cardio-protective mechanisms of the spices and their bioactive phytoconstituents using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these spices with special emphasis on their efficacy, safety, and toxicity.
Article
Full-text available
The rhizomes of ginger have been in use in many forms of traditional and alternative medicines. Besides being employed as condiment and flavoring agent, it is used in the treatment of nausea, osteoarthritis, muscle pain, menstrual pain, chronic indigestion, Alzheimer’s disease, and cancer. Ginger rhizome contains volatile oils, phenolic compounds and resins, and characterization studies showed that [6]-gingerol, [6]-shogaol, and [6]-paradol are reported to be the pharmacologically active components. Gingerol is a major chemical constituent found as volatile oil in the rhizomes of ginger. It has several medicinal benefits and used for the treatment of rheumatoid arthritis, nausea, cancer, and diabetes. Many studies have been carried out in various parts of the world to isolate and standardize gingerol for their use as a complementary medicine. The present review summarizes wide range of research studies on gingerol and its pharmacological roles in various metabolic diseases. Graphical Abstract
Article
Brefeldin A-ester (BAE) treatment significantly reduced SkBr3 and MDA-MB-231 cell proliferation in a concentration-dependent manner. It inhibited colony formation in SkBr3 and MDA-MB-231 cells significantly compared to the control cells. In BAE-treated MDA-MB-231 cells, migration and invasion potential showed a remarkable decrease after 72 h of incubation. Treatment with 12 µM of BAE led to a considerable suppression in MMP-2 and MMP-9 protein levels. The apoptotic cell fraction significantly increased in MDA-MB-231 cells at 72 h in comparison to the control cells. Treatment of MDA-MB-231 cells with BAE also caused a prominent suppression in expression of activated STAT3. Molecular docking studies revealed that BAE interacts with glutamic acid and tryptophan amino acids residues of STAT3 protein (4ZIA) through conventional H-bonding with binding affinity of − 9.6 kcal/mol at zero rmsd. Therefore, BAE treatment inhibits growth of breast cancer cells by targeting STAT3 phosphorylation and activation of apoptosis. BAE could have potential as a lead in the development of therapeutic agents for breast cancer.
Article
Traditional foods (TFs) inherit a long history and colorful cultures and are closely bound with the dietary patterns of indigenous people. They are either homemade or commercially made and purchased from local food outlets, which provide distinctive textural and sensory properties, nutritional values, and bioactivities. However, the science and wisdom of TFs are not necessarily clearly understood by local people in their historical context. Today's scientific knowledge and technical capabilities provide opportunities for scientists, industries, and consumers to understand the scientific ingenuity behind TFs, which may significantly promote the transition of TFs from homemade to scaled and standardized manufacturing with global availability and acceptance. In addition, the science of TFs may open new vistas for developing modern foods and new lifestyles. This review summarizes and provides insights into the science of TFs, covering food chemistry, food quality, food safety, health function, food processes, and its implications for future food systems.
Article
Full-text available
Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined.
Chapter
Natural products have been used to prevent and to treat various diseases from thousands of years. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to preventor cure cancer with affordable conditions. Several unfavourable side effects might arise with chemotherapy. Certain bioactive components from the plants have been used for their anticancer activities. These include curcumin, andrographolide, asiaticoside, phyllanthin, withaferin A, gingerol etc. In cancer therapy, using plant-derived compounds may help to reduce negative side effects. However, a myriad of many plant products exist that have shown very promising anti-cancer properties in vitro, but have yet to be evaluated for human’s use. Further study is required to determine the efficacy of these phytochemicals in treating cancers. In recent years, the various plants derived chemical compounds that have shown as anticancer agents and will outline their potential mechanism of action.
Chapter
Full-text available
Rhizomatous plants have been sources of remedy and were used widely as dietary spices and flavor. Their effects as immunomodulators are also documented. Several studies have confirmed that both Curcuma longa (turmeric) and Zingiber officinale (ginger) have a vast array of medicinal and immunomodulatory properties. Curcumin, which is one of the main curcuminoids of Curcuma longa, possesses various pharmacological properties, including immunomodulatory activities. Similarly, Zingiber officinale has a history of medicinal use for over 2500 years as one of the most versatile medicinal plants, which is traced to its bioactive compounds such as gingerol, paradol, shogaols, etc. The extracts and/or bioactive compounds from those plants are promising drug candidates against various diseases such as diabetes mellitus, bacterial infection, Alzheimer’s disease, rheumatoid arthritis, and cancer, partly via their immunomodulatory properties. Several studies have identified some of the bioactive compounds in Curcuma longa and Zingiber officinale rhizomes as potential inhibitors of the novel coronaviruses responsible for the COVID-19 pandemic. Such bioactive compounds are eligible for further investigation of the potential to treat COVID-19 patients effectively. This chapter describes the regulation of immune responses by rhizomatous Curcuma longa and Zingiber officinale for the treatment of diseases of diverse origin.KeywordsRhizomatous plantsImmunomodulator Curcuma longa CurcuminCoronavirus Zingiber officinale Gingerol
Article
Full-text available
Ginger is traditionally known for its therapeutic and pharmaceutical properties. It has been used widely to treat various health problems such as high blood pressure, coughs, colds, swelling, nausea, rheumatic disorders, vomiting, bronchitis, indigestion, gastric ulcers, and behavioral problems. Shogaol and Gingerol are anti-inflammatory, anti-fever, anti-pain, and anti-cough compounds that may help treat a cold. This review provides an up-to-date understanding of the impact of ginger and its active compounds on human health. Various ginger compounds such as gingerol, shogaols, zingiberene, zingerone, paradols and zingerone are receiving attention for their clinical applications and pharmaceutical properties. Studies indicate that ginger is anti-inflammatory, anti-tumor, antimicrobial, antiemetic, hepatoprotective, and neuroprotective. During the inflammatory response, ginger inhibits (NF-κB) and immune system activation in addition to many other cellular processes. Ginger has shown benefits in preclinical and clinical studies for neurology, cardiovascular disease, and cancer. These findings indicate the necessity for further in vivo and clinical studies.
Preprint
Full-text available
Ginger is traditionally known for its therapeutic and pharmaceutical properties. It has been used widely to treat various health problems such as high blood pressure, coughs, colds, swelling, nausea, rheumatic disorders, vomiting, bronchitis, indigestion, gastric ulcers, and behavioral problems. Shogaol and Gingerol are anti-inflammatory, anti-fever, anti-pain, and anti-cough compounds that may help treat a cold. This review provides an up-to-date understanding of the impact of ginger and its active compounds on human health. Various ginger compounds such as gingerol, shogaols, zingiberene, zingerone, paradols and zingerone are receiving attention for their clinical applications and pharmaceutical properties. Studies indicate that ginger is anti-inflammatory, anti-tumor, antimicrobial, antiemetic, hepatoprotective, and neuroprotective. During the inflammatory response, ginger inhibits (NF-κB) and immune system activation in addition to many other cellular processes. Ginger has shown benefits in preclinical and clinical studies for neurology, cardiovascular disease, and cancer. These findings indicate the necessity for further in vivo and clinical studies.
Article
Full-text available
The diagnosis and treatment of solid tumors usually begins at a late stage when most patients already have occult or overt metastasis. Many years of cancer progression precede diagnosis of most solid tumors. Novel noncytotoxic therapeutics may be specially suited for administration during this interval. An important window of intervention can be defined as the period during which transition from a hyperproliferative state to acquisition of the capacity for invasion and metastasis occurs. Investigation of the molecular basis of invasion is uncovering strategies for delaying progression of preinvasive carcinoma and treatment of primary tumors and established metastasis. Although tumor cell invasion might not be rate limiting for the growth of metastasis, anti-invasive agents can block tumor angiogenesis and thereby indirectly block metastasis growth. Two classes of molecular anti-invasion targets exist: (a) cell surface and extracellular proteins, which mediate sensing, adhesion, and proteolysis; and (b) signal transduction pathways, which regulate invasion, angiogenesis, and proliferation. Both categories of targets yield treatment approaches that are now being tested in the clinic. Metalloproteinase inhibitors, such as BB94, are based on the recognition that metalloproteinases play a necessary role in invasion and angiogenesis. The orally active signal transduction inhibitor carboxyamidotriazole modulates non-voltage-gated calcium influx-regulated signal pathways and reversibly inhibits tumor invasion, growth, and angiogenesis. Blockade of invasion, angiogenesis, or cellular signal pathways is likely to generate a cytostatic, rather than a cytotoxic effect. Cytostatic therapy constitutes an alternative paradigm for clinical translation that may complement conventional cytotoxic therapy. For patients with newly diagnosed solid tumors, long-term cytostatic therapy could potentially create a state of metastasis dormancy or delay the time to overt relapse following cytotoxic agent-induced remission. Clinical toxicity and pharmacology using oral cytostatic agents in phase I trials and in adjuvant settings will provide an important foundation for the translation of this approach to the preinvasive carcinoma period.
Article
Full-text available
Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality.
Article
Full-text available
Conjugated linoleic acid (CLA) has chemoprotective properties in experimental cancer models, and in vitro studies have shown that CLA inhibits HT-29 colon cancer cell growth. ErbB2 and ErbB3 have been implicated in the development of colon cancer, and both proteins are expressed at high levels in the HT-29 cell line. Activation of ErbB2/ErbB3 heterodimers is regulated by the ErbB3 ligand heregulin. To examine CLA regulation of HT-29 cell proliferation and apoptosis and the influence of CLA on the ErbB3 signaling pathway, HT-29 cells were cultured in the presence of CLA and/or heregulin. CLA inhibited DNA synthesis and induced apoptosis of HT-29 cells. Although the addition of heregulin-alpha led to an increase in cell number, it was not able to counteract the negative growth regulatory effect of CLA. Immunoprecipitation/Western blot studies revealed that CLA inhibited heregulin-alpha-stimulated phosphorylation of ErbB2 and ErbB3, recruitment of the p85 subunit of phosphoinositide 3-kinase (PI3-kinase) to the ErbB3 receptor, ErbB3-associated PI3-kinase activities, and phosphorylation of Akt. CLA decreased ErbB2 and ErbB3 mRNA and protein levels in a dose-dependent manner. In conclusion, we demonstrate that CLA inhibits cell proliferation and stimulates apoptosis in HT-29 cells and that this may be mediated by its ability to downregulate ErbB3 signaling and the PI3-kinase/Akt pathway.
Article
Many spices, including plants of the ginger family, possess anticarci- nogenic activity. However, the molecular mechanisms by which they exert their antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical role in tumor promotion, and blocking of tumor promoter- induced activation of AP-1 inhibits neoplastic transformation. Epidermal growth factor induces cell transformation and AP-1 activity. The purpose of this study was to investigate the effect of two structurally related compounds of the ginger family, (6)-gingerol and (6)-paradol, on EGF- induced cell transformation and AP-1 activation. Our results provide the first evidence that both block EGF-induced cell transformation but act by different mechanisms.
Article
Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
Article
The matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. The MMPs have been classified into different groups including collagenases, gelatinases, stromelysins, and others, particularly membrane-type MMPs, based mainly on the in vitro substrate specificity of individual MMPs. There is increasing evidence to indicate that individual MMPs have important roles in tumour invasion and metastasis. However, the current concept of the role of MMPs in tumour invasion is that they not only have a direct role in tumour invasion by facilitating extracellular matrix degradation, but as a consequence they also have an important role in maintaining the tumour micro-environment and thus promoting tumour growth. Inhibiting the action of MMPs represents a new therapeutic approach for the treatment of individual types of cancer and several broad-spectrum, low-molecular-weight MMP inhibitors are currently being assessed for clinical use. This review examines the role of MMPs in tumour invasion and metastasis, with an emphasis on studies of clinical relevance. Copyright © 1999 John Wiley & Sons, Ltd.
Article
Antioxidants minimize oxidation of the lipid components in foods. There is an increasing interest in the use of natural and/or synthetic antioxidants in food preservation, but it is important to evaluate such compounds fully for both antioxidant and pro-oxidant properties. The properties of thymol, carvacrol, 6-gingerol, hydroxytyrosol and zingerone were characterized in detail. Thymol, carvacrol, 6-gingerol and hydroxytyrosol decreased peroxidation of phospholipid liposomes in the presence of iron(III) and ascorbate, but zingerone had only a weak inhibitory effect on the system. The compounds were good scavengers of peroxyl radicals (CCl3O2; calculated rate constants > 106m−1 sec−1) generated by pulse radiolysis. Thymol, carvacrol, 6-gingerol and zingerone were not able to accelerate DNA damage in the bleomycin-Fe(III) system. Hydroxytyrosol promoted deoxyribose damage in the deoxyribose assay and also promoted DNA damage in the bleomycin-Fe(III) system. This promotion was inhibited strongly in the deoxyribose assay by the addition of bovine serum albumin to the reaction mixtures. Our data suggest that thymol, carvacrol and 6-gingerol possess useful antioxidant properties and may become important in the search for ‘natural’ replacements for ‘synthetic’ antioxidant food additives.
Article
Some 15 years ago there began to emerge a consensus among epidemiologists that diet might be responsible for 30-60% of cancers in the developed world, in the sense that it should be possible to reduce age-specific incidence rates by this amount by practicable dietary change. Within about 6 years it was also broadly agreed that the principal changes required to bring about this effect were a reduction in the consumption of fat; an increase in the consumption of fruit, green and yellow vegetables, dietary fiber, and some micronutrients; and possibly an improvement in the methods of food preservation. Very small effects, if any, were attributed to food additives and to the pollution of food by trace pesticides, which the public, who accepted much of the consensus advice, have increasingly regarded as important causes of risk. These past conclusions are reviewed in the light of increased knowledge of the etiology of cancer and the trends in its incidence. Contrary to common belief, the trends are broadly encouraging.
Article
One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis.
Article
Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration.
Article
The effects of onion and ginger consumption on platelet thromboxane production were examined. Volunteers, all Danish women, consumed either 70 g raw onion or 5 g raw ginger daily for a period of 7 days. Each participant in each (onion or ginger) group served as her own control. TxB2 determination was made in serum obtained after blood clotting. The following are the results. TxB2 (pmol/ml serum): (i) onion group--before consumption 910 +/- 327, after consumption 1005 +/- 713 (Mean +/- SD, N = 5); (ii) ginger consumption 782 +/- 482, after consumption 498 +/- 164 (Mean +/- SD, N = 7).
Article
One hundred twenty-one species of edible plants (133 test-parts) were screened against possible anti-tumor promoting activity by an in vitro short-term assay system of inhibition of Epstein-Barr virus (EBV) activation induced by a phorbol-ester promoter, 12-O-hexadecanoylphorbol-13-acetate (HPA). The methanol-extracts (ME) of 14 species of the edible plants strongly inhibited the activation, 7 moderately and 12 weakly inhibited it. On partition of the randomly selected inactive ME (26 species) with ethyl acetate and water, 13 and 2 species were active, more or less, in the ethyl acetate and water soluble part, respectively. Thus, this result suggested that anti-tumor promoters occur in a wide variety of edible plants. The anti-tumor promoting activity in the crude extracts may be enhanced or reduced with co-occurring factors acting additively, synergistically or antagonistically.
Article
Aqueous ginger extract was extracted in three organic solvents viz., n-hexane, chloroform and ethyl acetate with increasing polarity. The extracted materials from these solvents reduced platelet thromboxane formation from exogenous arachidonate (AA) and also inhibited platelet aggregation induced by AA, epinephrine, ADP and collagen; in this respect they were most effective against AA-induced aggregation. The extracted material in n-hexane was further resolved by thin-layer chromatography into various fractions some of which were effective in inhibiting platelet thromboxane formation and platelet aggregation. Aqueous ginger extract reduced the formation of TxB2 from AA-labelled platelets without showing effects on platelet phospholipase activity. Thromboxane formation in labelled platelets on activation with calcium ionophore A23187 was reduced by ginger components, isolated from two TLC bands, in a dose-dependent manner (10-100 ug/500 ml). At the higher dose lipoxygenase products were also reduced. Interestingly the incorporation of AA into platelet phospholipids increased in platelets treated with aqueous ginger extract.
Article
Tumour cells traverse epithelial and endothelial basement membranes during the successive stages of the metastatic process. At the transition from in situ to invasive carcinoma, local dissolution of the basement membrane is observed microscopically1,2, and coincides with tumour cell invasion of the underlying stroma. Tumour cells further traverse the endothelial basement membrane during entry into and egress from blood vessels3-5. Electron microscopic studies have shown local dissolution of basement membrane at its area of contact with invading tumour cells, suggesting an enzymatic mechanism3,6,7. Basement membranes are resilient structures which present a mechanical barrier to invasion8. Type IV collagen is a major structural protein of basement membranes and is chemically and genetically distinct from stroma collagen types I and III and cartilage collagen type II9,10. Previously characterised animal collagenases which cleave collagen types I; II and III fail to degrade type IV collagen11,12. We have recently purified about 1,000-fold and characterised a neutral protease activity preferential for type IV collagen from metastatic tumour cells and shown that it (1) produces specific degradation products, (2) has a molecular weight of 65,000, (3) is not plasmin or a cathepsin, by pH and inhibitor studies, and (4) does not significantly degrade other collagens or fibronectin12,13. Here we extend the relevance of this finding by quantitating the ability of several murine tumour cell lines of known metastatic potential to degrade type IV collagen. The cell lines with the highest incidence of spontaneous metastasis exhibit the greatest level of type IV collagen-degrading activity in two different assays using either living cells or media obtained from cell cultures.
Article
Aqueous extracts of onion, garlic and ginger inhibited platelet aggregation induced by several aggregation agents, including arachidonate (AA), in a dose-dependent manner. While onion and garlic extracts were found to be weak inhibitors of platelet thromboxane synthesis, ginger extract inhibited the platelet cyclooxygenase products and this effect correlated well with its inhibitory effects on the platelet aggregation induced by the above aggregation agents. These two effects were dose-dependent. Although the three aqueous extracts inhibited the biosynthesis of 6-keto-F1 alpha in rat aortic rings from labelled AA, they did not reduce prostacyclin production from endogenous AA pool in aortic rings. Aqueous ginger extract was extracted into three organic solvents in order of increasing polarity (n-hexane, chloroform, ethyl acetate). An analysis of the n-hexane extract revealed at least three clearly separated TLC bands containing materials that inhibited platelet thromboxane generation simultaneously increasing lipoxygenase products (HETE). The results indicate that if the same were happening in vivo, onion, garlic and ginger could be useful as natural antithrombotic materials.
Article
The study of integrin receptor expression and function in carcinomas will undoubtedly increase our understanding of the malignant process and clarify the relative importance of the numerous alterations that are identified. Whether this will lead to direct clinical applications is not clear at present, but it will certainly alter our approach to the evaluation of cancer treatment. The more immediate search for prognostic indicators and metastatic site preference in tumours expressing a particular integrin profile is partly hampered by the small numbers of cases studied in most series, where observed trends in tumour subsets barely achieve significance. Perhaps the next phase should be to evaluate promising approaches in large multicentre studies to establish the relative importance of these trends in tumour prognosis and response to treatment, preferably by developing reagents that will permit the demonstration of integrins in routinely processed archival material from human tumour specimens. Future developments in therapy may depend on the knowledge that may emerge from such work.
Article
The purpose of this investigation was to determine the antiplatelet mechanism of gingerol. Gingerol concentration-dependently (0·5–20 μm) inhibited the aggregation and release reaction of rabbit washed platelets induced by arachidonic acid and collagen, but not those induced by platelet-activating factor (PAF), U46619 (9,11-dideoxy-9α,11 α-methano-epoxy-PGF2α) and thrombin. Gingerol also concentration-dependently (0·5–10μ m) inhibited thromboxane B2 and prostaglandin D2 formation caused by arachidonic acid, and completely abolished phosphoinositide breakdown induced by arachidonic acid but had no effect on that of collagen, PAF or thrombin even at concentrations as high as 300 μ m. In human platelet-rich plasma, gingerol and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by adenosine 5′-diphosphate (ADP, 5 μ m) and adrenaline (5 ä m) but had no influence on the primary aggregation. The maximal antiplatelet effect was obtained when platelets were incubated with gingerol for 30 min and this inhibition was reversible. It is concluded that the antiplatelet action of gingerol is mainly due to the inhibition of thromboxane formation.
Article
This study examined the effect of eugenol and ginger oil on severe chronic adjuvant arthritis in rats. Severe arthritis was induced in the right knee and right paw of male Sprague-Dawley rats by injecting 0.05 ml of a fine suspension of dead Mycobacterium tuberculosis bacilli in liquid paraffin (5 mg/ml). Eugenol (33 mg/kg) and ginger oil (33 mg/kg), given orally for 26 days, caused a significant suppression of both paw and joint swelling. These findings suggest that eugenol and ginger oil have potent antiinflammatory and/or antirheumatic properties.
Article
In summary there is a wealth of information on dietary and nutritional effects on carcinogenesis in laboratory rodents. Experimental studies based on epidemiological evidence, earlier experimental studies and known or predicted cellular, biochemical and molecular effects of nutrients have produced clear evidence that carcinogenesis in laboratory rodents is influenced by dietary intake of calories, fat, lipotropes (choline, methionine), vitamin A and related retinoids, Se, calcium, zinc, fiber, ethanol and a large number of non-nutrient components of foods. For these substances or groups of substances mechanistic hypotheses supported by experimental data and are leading to further research. The information provided will contribute to understanding of basic processes in carcinogenesis as well as of the specific interactions studied, and should contribute to significant advances in preventive medicine. Restriction of caloric intake of rodents by amounts > 10% over a significant portion of their lifetime reduces tumorigenesis. That level of restriction reduces the rate of growth and maturation, and most experiments in this area employ greater restrictions that virtually abolish growth from a young age. Therefore, the observations are of interest in mechanistic studies, but their applicability to preventive medicine requires better definition of the degree and duration of restriction required for a significant effect and the age at which it must be imposed. Restriction of total fat intake and modifications to increase the intake of omega-3 fats have a reasonably consistent effect on tumorigenesis in rodents but a much less consistently demonstrable effect in humans. Again, the observations in rodents are providing a major stimulus to mechanistic studies. The lipotropes are extremely valuable as tools for investigating mechanisms of carcinogenesis in rodents. Their importance in the epidemiology of human cancer has yet to be demonstrated clearly and is a subject of research at present. The naturally occurring vitamins and minerals, as well as fiber, derive their importance in this context from investigations to explain the consistent epidemiological demonstrations of reduction of tumor risk with increased consumption of fruits and vegetables. The activity of the isolated nutrients as anticarcinogens in rodents has generally not matched the activity expected from epidemiological studies. The anticarcinogenic activity of many of the non-nutrient components of fruits and vegetables is remarkable in particular models, however, as is the activity of natural and synthetic retinoids. At present the results must be interpreted to indicate an important effect of combinations of the whole foods with identification of particular nutrients or non-nutrients in specific cases.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Recent findings have produced great strides in developing an understanding of the molecular events involved in processes necessary for tumor cell invasion and subsequent metastasis formation. This information has been useful in developing new targets for therapeutic intervention such as disruption of tumor cell attachment by peptide analogues of cell adhesion molecules and the use of protease inhibitors to limit extracellular matrix proteolysis required for tumor cell invasion. Future efforts must focus on how the events of cell attachment, matrix proteolysis, and cell migration are controlled and integrated. This requires a better understanding of the transcriptional controls and cell signaling mechanisms that are involved in these events. Preliminary findings suggest that cell-matrix interactions influence gene expression and that the protease inhibitor balance can greatly influence cell-matrix interactions. Therefore it appears that all three steps in the invasive process are linked and interdependent. While this complicates the study of these processes, it is our belief that understanding this interdependence is critical for further development of metastasis research.
Article
There is considerable emphasis on identifying potential chemopreventive agents present in food consumed by the human population. Ginger rhizome (Zingiber officinale), known commonly as ginger, is consumed worldwide in cookeries as a spice and a flavoring agent. In prior in vitro studies, it has been shown that the water or organic solvent extract of ginger possesses antioxidative and antiinflammatory properties. In this study, we evaluated whether ethanol extract of ginger (GE) possesses anti-tumor-promoting effects in a mouse skin tumorigenesis model. Because skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hyperplasia are conventionally used markers of skin tumor promotion, first, we assessed the effect of GE on these parameters. Preapplication of GE onto the skin of SENCAR mice resulted in significant inhibition of 12-0-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epidermal ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expression in a does-dependent manner. Preapplication of GE to mouse skin also afforded significant inhibition of TPA-caused epidermal edema (56%) and hyperplasia (44%). In long-term tumor studies, topical application of GE 30 min prior to that of each TPA application to 7,12-dimethylbenz(a)anthracene-initiated SENCAR mice resulted in a highly significant protection against skin tumor incidence and its subsequent multiplicity. The animals pretreated with GE showed substantially lower tumor body burdens compared with non-GE-treated controls. The results of our study, for the first time, provide clear evidence that GE possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-caused cellular, biochemical, and molecular changes in mouse skin.
Article
Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell-matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.
Article
A wide array of phytochemicals have been shown to possess potential cancer chemopreventive properties. Ginger contains pungent phenolic substances with pronounced antioxidative and antiinflammatory activities. In the present study, we have determined the antitumor promotional activity of [6]-gingerol, a major pungent principle of ginger, using a two-stage mouse skin carcinogenesis model. Topical application of [6]-gingerol onto shaven backs of female ICR mice prior to each topical dose of 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly inhibited 7,12-dimethylbenz[a]anthracene-induced skin papillomagenesis. The compound also suppressed TPA-induced epidermal ornithine decarboxylase activity and inflammation.
Article
A large and increasing number of patients use medicinal herbs or seek the advice of their physician regarding their use. More than one third of Americans use herbs for health purposes, yet patients (and physicians) often lack accurate information about the safety and efficacy of herbal remedies. Burgeoning interest in medicinal herbs has increased scientific scrutiny of their therapeutic potential and safety, thereby providing physicians with data to help patients make wise decisions about their use. This article provides a review of the data on 12 of the most commonly used herbs in the United States. In addition, we provide practical information and guidelines for the judicious use of medicinal herbs.
Article
[6]-Gingerol, a major pungent ingredient found in the rhizome of ginger, has been reported to possess a strong antiinflammatory activity, which is considered to be closely associated with its cancer chemopreventive potential. [6]-Paradol, another pungent phenolic substance found in ginger and other Zingiberaceae plants, also has a vanilloid structure found in other chemopreventive phytochemicals including curcumin. In the present study, [6]-gingerol and [6]-paradol were found to exert inhibitory effects on the viability and DNA synthesis of human promyelocytic leukemia (HL-60) cells. The cytotoxic and antiproliferative effects of both compounds were associated with apoptotic cell death. The above results suggest that [6]-gingerol and [6]-paradol possess potential cytotoxic/cytostatic activities.
Article
Metastatic disease is responsible for the majority of cancer-related deaths, either directly due to tumor involvement of critical organs or indirectly due to complications of therapy to control tumor growth and spread. An understanding of the mechanisms of tumor cell invasion and metastasis may be important for devising therapies aimed at preventing tumor cell spread. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteinases whose enzymatic activity is directed against components of the extracellular matrix (ECM). In humans, 16 members of this family have been identified by cloning and sequencing. These proteinases are linked by a core of common domain structures and by their relationship to a family of proteinase inhibitors called the tissue inhibitors of metalloproteinases (TIMPs). Four members of the TIMP family have been cloned and sequenced in humans and they inhibit MMPs by forming tight-binding, noncovalent associations with the active site of the MMPs. MMPs facilitate tumor cell invasion and metastasis by at least three distinct mechanisms. First, proteinase action removes physical barriers to invasion through degradation of ECM macromolecules such as collagens, laminins, and proteoglycans. This has been demonstrated in vitro through the use of chemoinvasion assays and in vivo by the presence of active MMPs at the invasive front of tumors. Second, MMPs have the ability to modulate cell adhesion. For cells to move through the ECM, they must be able to form new cell-matrix and cell-cell attachments and break existing ones. Using a cell transfection system that altered the ratio of MMP-2 to TIMP-2 we have demonstrated significant variation in the adhesive phenotype of tumor cells. Finally, MMPs may act on ECM components or other proteins to uncover hidden biologic activities. For example, the angiogenesis inhibitor angiostatin may be produced from plasminogen by MMP action and laminin-5 is specifically degraded by MMP-2 to produce a soluble chemotactic fragment. Thus MMPs play multiple key roles in facilitating the metastasis of tumor cells. Therapies designed to interfere with specific MMP actions may be useful in the control of metastatic disease.
Article
The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, whose physiological functions include tissue remodelling and embryogenesis. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged, and has led to the search for MMP inhibitors for use as anticancer treatments in a clinical setting. This review aims to bring the reader up-to-date with current research relating to MMPs, with particular emphasis on emerging mechanisms of regulation of these enzymes, and their interaction with cell adhesion molecules. The therapeutic inhibition of MMPs will also be discussed.
Article
Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Antibodies to the adhesion molecules CD44, E-cadherin, ICAM- 1, and integrin chains alpha2, alpha3, alpha4, alpha5, alpha6, alpha v, beta1, beta3 and beta7 failed to inhibit breast cancer cell migration through bone marrow fibroblasts. Inhibitors of matrix metalloproteases, 1, 10-phenanthroline, Ro-9790, TIMP-1 and TIMP-2 were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts. Modulation of MMP production by cell-cell contact or soluble factors suggests a mechanism by which breast cancer cells can enhance their ability to invade the bone marrow microenvironment.
Article
Selenium, an essential biological trace element, has been shown to reduce and prevent the incidence of cancer. Our previous studies have shown that selenite is involved in the chemoprevention of cancer and induction of apoptosis of cancer cells. In this study, we demonstrate that selenite also inhibits the invasion of tumor cells. Cancer cell invasion requires coordinated processes, such as changes in cell-cell and cell-matrix adhesion, degradation of the extracellular matrix, and cell migration. We found that selenite inhibited invasion of HT1080 human fibrosarcoma cells. Adhesion of HT1080 cells to the collagen matrix was also inhibited by treatment with selenite, but cell-cell interaction and cell motility were not affected by selenite. Moreover, selenite reduced expression of matrix metalloproteinase-2 and -9 and urokinase-type plasminogen activator, which are involved in matrix degradation, but increased a tissue inhibitor of metalloproteinase-1. This inhibitory effect of selenite on the protease expressions was mediated by the suppression of transcription factors, NF-κB and AP-1. However, selenate showed no remarkable effect on all the steps of cancer cell invasion.
Article
As our understanding of the development of cancer and the complex signalling mechanisms involved improves, we are beginning to appreciate the enormous potential for intervention strategies that prevent or slow down the disease process. Although much research is currently aimed at developing drugs to target key molecules in tumour cells that are responsible for their proliferation and survival, dietary constituents also have potential as anti-cancer agents. Our goal should be not only to identify carcinogenic changes as early as possible and to intervene effectively long before life-threatening tumours develop, but also to understand how a balanced, healthy diet can contribute to reduced incidence, as epidemiology so tantalizingly suggests.
Article
Botanicals have been used for the treatment of various human diseases throughout history. In addition, botanicals play a role in disease prevention. For example, epidemiologic studies have suggested that a reduced risk of cancer is associated with high consumption of vegetables and fruits. Thus, the cancer chemopreventive potential of naturally occurring phytochemicals is of great interest. In this review, we discuss the cancer chemopreventive activity of cruciferous vegetables such as cabbage and broccoli, Allium vegetables such as garlic and onion, green tea, Citrus fruits, tomatoes, berries, ginger and ginseng, as well as some medicinal plants. In addition, methods for the discovery of active compounds from plant sources are described. Several lead compounds, such as brassinin (from cruciferous vegetables like Chinese cabbage), sulforaphane (from broccoli) and its analog sulforamate, withanolides (from tomatillos), and resveratrol (from grapes and peanuts among other foods), are in preclinical or clinical trials for cancer chemoprevention. Phytochemicals of these types have great potential in the fight against human cancer, and a variety of delivery methods are available as a result of their occurrence in nature.
Article
Antimutagens and anticarcinogens are common amongst many traditional herbal remedies and dietary therapies. With increased understanding of the mechanistic basis of cancer development and cancer prevention, we are now better aware of ways in which some of these traditional remedies may act at the cellular or subcellular levels. This special issue features some of the highlights of the conference on this topic that was held in Seoul on October 17-19, 2001.
Article
Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental cancer models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine in rats. In addition, our in vitro studies have shown that CLA inhibits DNA synthesis and induces apoptosis in HT-29 cells, the human colon adenocarcinoma cell line. The insulin-like growth factor (IGF) system regulates the growth of HT-29 cells by an autocrine mechanism. The present study examined whether the growth inhibitory effect of CLA is related to changes in the IGF system in HT-29 cells. To determine whether CLA inhibits IGF-II production, HT-29 cells were incubated in serum-free medium in the presence of various concentrations of CLA. CLA decreased protein levels of both mature and pro IGF-II and IGF-II transcripts. Whereas exogenous IGF-I and IGF-II produced an increase in cell number, neither IGF-I nor IGF-II counteracted the negative growth regulatory effect of CLA. Reverse transcriptase-polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased IGF-I receptor (IGF-IR) transcript and protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that CLA inhibited IGF-I-induced phosphorylation of IGF-IR and insulin-receptor substrate (IRS)-1, recruitment of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to IGF-IR, IGF-IR-associated PI3K activity, and phosphorylated Akt and extracellular signal-regulated kinase (ERK)-1/2 levels. In conclusion, the inhibition of cell proliferation and induction of apoptosis by CLA in HT-29 cells may be mediated in part by its ability to decrease IGF-II synthesis and to downregulate IGF-IR signaling and the PI3K/Akt and ERK-1/2 pathways.
Article
Flaxseed has been shown to reduce the metastasis of estrogen receptor negative (ER-) human breast cancer in nude mice. This study determined whether enterodiol (ED) and enterolactone (EL), metabolites of plant lignans exceptionally rich in flaxseed, and tamoxifen (TAM), alone or in combination, can influence the various steps of metastasis, that is, breast cancer cell adhesion, invasion and migration, of two ER- human breast cancer cell lines, MDA-MB-435 and MDA-MB-231. The inhibition by ED, EL or TAM (1-5 microM) of cell adhesion to Matrigel or extracellular matrices, fibronectin, laminin, and type IV collagen, as well as cell invasion was dose dependent in both cell lines. When ED, EL and TAM were combined at 1 microM, a greater inhibitory effect on cell adhesion and invasion was observed than with either compound alone. ED and EL at doses of 0.1-10 microM reduced cell migration, but TAM had no effect at 0.1 and 1 microM, and exhibited a stimulatory effect at 10 microM. It is concluded that lignans and TAM, alone or in combination, can inhibit the steps involved in the metastasis cascade. Although more investigations are required, the study also suggests that the intake of the lignan-rich flaxseed may not antagonize the effect of TAM in ER- breast cancer cells.
Article
Various proteases are involved in cancer progression and metastasis. In particular, gelatinases, matrix metalloproteinase-2 (MMP-2) and MMP-9, have been implicated to play a role in colon cancer progression and metastasis in animal models and patients. In the present review, the clinical relevance and the prognostic value of messenger ribonucleic acid (mRNA) and protein expression and proenzyme activation of MMP-2 and MMP-9 are evaluated in relation to colorectal cancer. Expression of tissue inhibitors of MMPs (TIMPs) in relation with MMP expression in cancer tissues and the relevance of detection of plasma or serum levels of MMP-2 and/or MMP-9 and TIMPs for prognosis are also discussed. Furthermore, involvement of MMP-2 and MMP-9 in experimental models of colorectal cancer is reviewed. In vitro studies have suggested that gelatinase is expressed in cancer cells but animal models indicated that gelatinase expression in non-cancer cells in tumors contributes to cancer progression. In fact, interactions between cancer cells and host tissues have been shown to modulate gelatinase expression in host cells. Inhibition of gelatinases by synthetic MMP inhibitors has been considered to be an attractive approach to block cancer progression. However, despite promising results in animal models, clinical trials with MMP inhibitors have been disappointing so far. To obtain more insight in the (patho)physiological functions of gelatinases, regulation of MMP-2 and MMP-9 expression is discussed. Mitogen activated protein kinase (MAPK) signalling has been shown to be involved in regulation of gelatinase expression in both cancer cells and non-cancer cells. Expression can be triggered by a variety of stimuli including growth factors, cytokines and extracellular matrix (ECM) components. On the other hand, MMP-2 and MMP-9 activity regulates bioavailability and activity of growth factors and cytokines, affects the immune response and is involved in angiogenesis. Because of the multifunctionality of gelatinases, it is unpredictable at what stage of cancer development and in which processes gelatinase activity is involved. Therefore, it is concluded that the use of MMP inhibitors to treat cancer should be considered carefully.
Article
Ginger (Zingiber officinale Roscoe) shows an antioxidant activity, and we have been engaging to determine the structures of more than 50 antioxidants isolated from the rhizomes of ginger. The isolated antioxidants are divided into two groups; gingerol related compounds and diarylheptanoids. In this study, structure-activity relationship of gingerol related compounds was evaluated. Gingerol related compounds substituted with an alkyl group bearing 10-, 12- or 14-carbon chain length were isolated from the dichloromethane extract of rhizomes using repeated chromatographic techniques. The antioxidant activities of these compounds were evaluated by the following measurements; 1) 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, 2) inhibitory effect on oxidation of methyl linoleate under aeration and heating by the Oil Stability Index (OSI) method, and 3) inhibitory effect on oxidation of liposome induced by 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH). These results suggested that the substituents on the alkyl chain might contribute to both radical scavenging effect and inhibitory effect of autoxidation of oils, while inhibitory effects against the AAPH-induced peroxidation of liposome was somewhat influenced by the alkyl chain length; the antioxidant activity might be due to not only radical scavenging activity of antioxidants but also their affinity of the antioxidants to the substrates.
Article
Ginger is one of the most widely used spices and has been used in traditional oriental medicines for long time. Its extract and major pungent principles have been shown to exhibit a variety of biological activities. In order to find more active constituents and evaluate their structure-activity relationship (SAR) we isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe) five new diarylheptanoids along with 20 known diarylheptanoids and gingerol-related compounds and studied their cytotoxic and apoptotic activities against human promyelocytic leukemia (HL-60) cells. It was found that compounds 1a, 2a, 5, 6a, 6b and 7 possess significant cytotoxicity against HL-60 cells (IC(50)<50 microM) and that the cytotoxic activity is associated with the cell apoptosis. SAR analysis demonstrates that the following structural determinants contribute critically to the enhancement of the activity: (i) acetoxyl groups at 3- and/or 5-positions of the side chain; (ii) the appropriate longer alkyl side-chain length; (iii) the ortho-diphenoxyl functionality on the aromatic ring; (iv) the alpha,beta-unsaturated ketone moiety in the side chain. These provide useful information for potential chemopreventive drug design.
Article
[6]-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has anti-bacterial, anti-inflammatory, and anti-tumor-promoting activities. Here, we describe its novel anti-angiogenic activity in vitro and in vivo. In vitro, [6]-gingerol inhibited both the VEGF- and bFGF-induced proliferation of human endothelial cells and caused cell cycle arrest in the G1 phase. It also blocked capillary-like tube formation by endothelial cells in response to VEGF, and strongly inhibited sprouting of endothelial cells in the rat aorta and formation of new blood vessel in the mouse cornea in response to VEGF. Moreover, i.p. administration, without reaching tumor cytotoxic blood levels, to mice receiving i.v. injection of B16F10 melanoma cells, reduced the number of lung metastasis, with preservation of apparently healthy behavior. Taken together, these results demonstrate that [6]-gingerol inhibits angiogenesis and may be useful in the treatment of tumors and other angiogenesis-dependent diseases.
Article
Matrix metalloproteinases (MMPs) are involved in extracellular matrix modification and associated with invasive and metastatic behavior of human malignant tumors. Specifically, MMP2 and MMP9 are implicated in both early and late processes of tumor development. It is reported that MMPs occur as inactive precursors, active enzymes or enzyme inhibitor complexes in b