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Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells
Abstract
Garlic (Allium sativum) has been used for centuries for treating various ailments, and its consumption is said to reduce cancer risk and its extracts and components effectively block experimentally induced tumors. Allicin, the major component present in freshly crushed garlic, is one of the most biologically active compounds of garlic. We found that allicin inhibited the growth of cancer cells of murine and human origin. Allicin induced the formation of apoptotic bodies, nuclear condensation and a typical DNA ladder in cancer cells. Furthermore, activation of caspases-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase were induced by allicin. The present results demonstrating allicin-induced apoptosis of cancer cells are novel since allicin has not been shown to induce apoptosis previously. Our results also provide a mechanistic basis for the antiproliferative effects of allicin and partly account for the chemopreventive action of garlic extracts reported by earlier workers.
... [62][63][64], anti-fungal [63], and viral properties [65]. It exhibits antihypertensive [66] and neuroprote properties [67] and acts as hypo-lipid and hypo-glycemic [68,69] and anti-c agent [70][71][72]. ...
... It embodies free radical scavenging properties, viz., anti-oxidant [61], antibacterial [62][63][64], anti-fungal [63], and antiviral properties [65]. It exhibits antihypertensive [66] and neuroprotective properties [67] and acts as hypo-lipidemic and hypo-glycemic [68,69] and anti-cancer agent [70][71][72]. ...
... Moreover, it has been demonstrated to inhibit cholesterol biosynthesis seemingly owing to the inhibition of squalene-monooxygenase 85 and acetyl-CoA synthetase [68,69,163,164]. It has displayed intriguing anticancer potential against different types of cancers [70][71][72]. Moreover, it has been shown to exhibit an antihypertensive effect and neuroprotective potentials as well [66]. ...
Simple Summary
Over the years, alternative and complementary medicine have garnered much attention all across the globe. To this end, phytochemicals have intriguing potential against myriads of disease conditions; nevertheless, as of yet, the molecular intricacies for their therapeutic potential is incompletely understood. It is widely acknowledged that proteomics technology has been ex-plored as a reliable approach to understand the molecular intricacies related to phytochemi-cal-based therapeutic interventions. Reckoning with this, the present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Curcumin, Genistein, and Tanshinone IIA.
Abstract
Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.
... The key apoptotic proteins caspase-3, caspase-8, and caspase-9 play crucial roles in suppressing autophagy and facilitating apoptosis [15]. Allicin induces a redox shift in human cell cultures, activating both caspase-dependent and independent apoptotic pathways [16]. ...
... Allicin's cytotoxic effects have been well-documented across various human cancer cell lines, including glioma U87, liver cancer G2, and gastric cancer MGC803 [23,24]. Allicin has been shown to enhance apoptosis and facilitate DNA ladder formation in cancer cells [16]. In vitro studies in 2021 involving MCF-7 Fig. 7 Gene expression analysis of tumor apoptosis markers: Expression levels of caspase-3, caspase-8, and caspase-9 were compared in A549 cells. ...
Solid lipid nanoparticles (SLNs) represent a promising alternative to traditional colloidal drug delivery systems. This study aimed to develop allicin-loaded SLNs and evaluate their cytotoxic and apoptotic effects on A549 lung cancer cells and normal HFF cells. Allicin was incorporated into SLNs using a high-pressure homogenization method with stearic acid and Tween 80 lecithin. The cytotoxicity of these nanoparticles was assessed using flow cytometry and gene expression analysis of key apoptotic markers. The expression levels of caspase-3, caspase-8, and caspase-9, which are central to the apoptotic process, were evaluated in A549 cells and compared to normal cells to determine the apoptotic potential of the nanoparticles. The inhibitory power of the synthesized nanoparticle against ABTS and DPPH free radicals was evaluated. The developed nanoparticles had a size of 67.01 nm and a surface charge of − 29.29 mV. Treatment with the nanoparticles significantly reduced the viability of A549 cells after 48 h, while normal HFF cells remained unaffected. The EC50 value for the nanoparticles was approximately 32 μg/ml. Flow cytometry revealed an increase in the subG1 peak, indicating the induction of apoptosis. The nanoparticles upregulated caspase-3 and caspase-9 but had minimal effect on caspase-8. SLN has an inhibitory effect on ABTS and DPPH free radicals. These findings suggest that allicin-loaded SLNs are a promising therapeutic approach for cancer treatment, as they effectively inhibit the proliferation of cancer cells while sparing normal cells.
... Allicin hampered the growth of murine and human malignant cells and induced their apoptosis [29][30][31]. This compound prevented the induction of gastric cancer as well [32]. ...
... Gallic acid is also a compound strongly inhibiting the proliferation of malignant cells and is considered to be a potential anticancer agent [77]. The IC 50 values of gallic acid for P388-D1 mouse lymphoid cancer cells, HL-60RG cells human promyelocytic leukemia cells, HeLa human epithelial carcinoma cells, dRLh-84 rat hepatoma cells, PLC/PRF/5 human hepatoma cells, and KB human epidermoid carcinoma cells were reported to be 4.8, 5.4, 6.1, 6.2, 6.6, and 13.2 µg/mL (27,30,34,34,37, and 73 µM), respectively [78], while other authors found IC 50 values of gallic acid for HeLa and HTB-35 cervical cancer cells between 20 and 25 µg/mL (111-139 µM) [79]. The IC 50 values at 48 h exposure were 16, 21, and 16 µg/mL (89,117, and 89 µM) for DUI45, LNCaP, and PC-3 prostate cancer cells, respectively [80]. ...
Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.
... One of these compounds is allicin which is a potent bioactive in garlic [4]. Its antitumor potential is reported in a variety of tumor types [5]. Furthermore, antibacterial [6], cholesterollowering [7], anti-inflammatory [8], and antiviral activities of allicin are also described [9]. ...
... The potential of allicin to cause apoptosis was considered to be the cause of its anticancer effects [56]. Apoptosis can occur through various pathways, including both caspase-dependent [5] and caspase-independent pathways [57]. Apoptosis-inducing factor (AIF), the first mitochondrial-released protein, regulates caspase-independent apoptosis and promotes chromatin condensation and DNA deterioration [58]. ...
Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.
... It is used as a seasoning or in the preparation of chili sauces. 4) Citrus garlic vinegar: This vinegar is produced by fermenting garlic mixed with citrus fruit (e.g., lemons or oranges); it features both garlic avors and a tangy sweetness. ...
... 1.4 Effects of garlic enzymes on human health [3][4] The primary impacts of garlic enzymes on the human body are as follows. 1) Antimicrobial properties: Garlic enzymes have considerable antimicrobial properties; they are effective against various bacteria, viruses, and fungal infections. ...
Garlic is a widely cultivated crop that contains numerous chemical compounds with health benefits. Both magnesium and zinc are essential nutrients for the human body. Increasing the magnesium content in garlic could stabilize the allicin enzyme, preventing its decomposition or release. Moreover, increasing the zinc content in garlic could enhance its antioxidative properties and health benefits; additionally, zinc plays a vital role in the synthesis of various hormones. In this study, we powdered serpentine derived from natural sources and treated it by microwaving and sintering to enhance its crystallinity as well as its magnesium and zinc ion release rates. The powder was then used to produce a magnesium–zinc solution for cultivating garlic. The growth and garlic enzyme activity of the garlic were then examined. The results revealed that microwaving and sintering the serpentine powder reduced its impurities, enhanced its crystallinity (including surface area), and increased the magnesium and zinc ion release rates. When the cultivation solution was prepared using the powder that was microwaved and then sintered (400°C for 1 h), it exhibited the same beneficial properties as if the solution had been prepared with natural magnesium and zinc ions. The enriched garlic contained 32–41 mg/L of magnesium and10-15 mg/L of zine. It also exhibited more garlic glands and higher sulfide content compared with regular garlic. After air drying, the garlic glands of the enriched garlic remained intact and had high moisture content, indicating its high nutritional value and antioxidative properties. Furthermore, an enriched garlic enzyme extract had an approximately 8-fold increase in alliinase activity compared with an unenriched extract.
... Most of its species' grow in the mountainous region of Tien Shan and Pamir-Alay westwards across Afghanistan and Iran to Turkey (Djavadi and Attar, 2009). About 210-250 species of Cousinia grow in Iran with (Lamm and Riggs, 2000;Shirzad et al., 2011;Herman-Antosiewicz and Singh, 2004;Shukla and Kalra, 2007;Hadjzadeh et al., 2006;Nakagawa et al., 2001;Oommen et al., 2004) (Al-Snafi, 2013; Maleki et al., 2013;Pakfetrat et al., 2015;Abdul-Jalil et al., 2010) Astrodaucus orientalis (L.) Drude. ...
... Garlic also increased the cytokines production of interleukin (IL)− 2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α that are associated with T helper (Th)l antitumor response (Lamm and Riggs, 2000). Other studies also demonstrated the antitumor activity of garlic against various solid tumors, such as breast, hepatoma, stomach, colon and prostate cancers, as well as leukemic cells in in vitro or animal models, by various mechanisms (Hadjzadeh et al., 2006;Herman-Antosiewicz and Singh, 2004;Nakagawa, Hiroyuki et al., 2001;Oommen et al., 2004;Shukla and Kalra, 2007). The major anticancer activities include growth inhibition, cell cycle arrest, apoptosis (caspase activation, upregulation of pro-apoptotic molecules and downmodulation of anti-apoptotic agents), antimutagenic activities, chemoprevention, modulating the activity of metabolizing enzymes, detoxifying carcinogens, inhibiting DNA adduct formation, antioxidative and free radicals scavenging activities, regulation of cell proliferation and immune responses and modulating cell-signaling pathways (Table 1). ...
... Most of its species' grow in the mountainous region of Tien Shan and Pamir-Alay westwards across Afghanistan and Iran to Turkey (Djavadi and Attar, 2009). About 210-250 species of Cousinia grow in Iran with (Lamm and Riggs, 2000;Shirzad et al., 2011;Herman-Antosiewicz and Singh, 2004;Shukla and Kalra, 2007;Hadjzadeh et al., 2006;Nakagawa et al., 2001;Oommen et al., 2004) (Al-Snafi, 2013; Maleki et al., 2013;Pakfetrat et al., 2015;Abdul-Jalil et al., 2010) Astrodaucus orientalis (L.) Drude. ...
... Garlic also increased the cytokines production of interleukin (IL)− 2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α that are associated with T helper (Th)l antitumor response (Lamm and Riggs, 2000). Other studies also demonstrated the antitumor activity of garlic against various solid tumors, such as breast, hepatoma, stomach, colon and prostate cancers, as well as leukemic cells in in vitro or animal models, by various mechanisms (Hadjzadeh et al., 2006;Herman-Antosiewicz and Singh, 2004;Nakagawa, Hiroyuki et al., 2001;Oommen et al., 2004;Shukla and Kalra, 2007). The major anticancer activities include growth inhibition, cell cycle arrest, apoptosis (caspase activation, upregulation of pro-apoptotic molecules and downmodulation of anti-apoptotic agents), antimutagenic activities, chemoprevention, modulating the activity of metabolizing enzymes, detoxifying carcinogens, inhibiting DNA adduct formation, antioxidative and free radicals scavenging activities, regulation of cell proliferation and immune responses and modulating cell-signaling pathways (Table 1). ...
Introduction
The increasing number of cancer patients, together with the side effects of current chemical treatments have encouraged the exploration of the potential of Iranian medicinal plants as a rich source of anticancer compounds.
Methods
In the current review, 114 medicinal plant species grown in Iran were selected and their major constituents, animal or cell targets, as well as possible anticancer mechanisms, were ascertained through searching pertinent keywords in the Scientific Information Database (SID), IranMedex, PubMed, Medline, Google Scholar, Science Direct, Web of Knowledge and Scopus databases.
Results
Of the 114 species (with more emphasis on Asteraceae, Lamiaceae and Fabaceae as major plant families in Iran) that were reviewed, some were endemic plants of Iran, with others found in other countries. Besides valuable and well-known anticancer plants such as Taxus baccata and Catharanthus roseus, other species were included. Several compounds of these plants, such as organo-sulfur compounds, terpenoids, polyphenols, alkaloids, saponins, phenylethanoids, coumarins and polysaccharides have been proposed to exhibit anticancer effects. In general, apoptosis, cytotoxicity, cell cycle arrest, mitochondrial suppression, reductiob of DNA damage, vital enzyme inhibition and/or blocking angiogenesis were considered as the proposed mechanisms for the anticancer potential of the studied plants.
Conclusion
Investigating the bioactive anticancer components of Iranian medicinal plants, especially the endemic species, seems to be beneficial for achieving novel potential anticancer drugs that are better equipped to fight cancer.
... 32 Caspase-3 is an effector caspase that forms the junction point in the pathway of apoptosis in various pathways (Fas L death ligand or any apoptotic stimulus via bcl-2). 13 Oommen et al. (2004) reported that allicin triggered the formation of apoptotic bodies by triggering cleavage of poly (ADPribose) polymerase and activation of caspase 3.8.9. and inhibited the growth of cancer cells of murine and human origin. 33 In their study Gore et al. (2021) determined that due to allin and allicin in the structure of garlic. ...
... 13 Oommen et al. (2004) reported that allicin triggered the formation of apoptotic bodies by triggering cleavage of poly (ADPribose) polymerase and activation of caspase 3.8.9. and inhibited the growth of cancer cells of murine and human origin. 33 In their study Gore et al. (2021) determined that due to allin and allicin in the structure of garlic. it showed breast. ...
Garlic (Allium sativum) is a spice used for
centuries for both condiment and medicinal purposes.
Studies have shown that it has antibacterial, antiviral,
anti-inflammatory, antifungal, antimutagenic,
antioxidant, antiallergic, anti-aging, antitumoral and
immunostimulatory activities. Activation of caspase3 initiates the caspase activation chain, leading to
apoptosis. In this study aimed to determine the
apoptotic effect of DMSO-containing aged garlic
extracts (AGE) on Myoid Cancer Cell lines (HL-60).
Flow cytometry method and spectrophotometric
caspase-3 activity analyzes were used using human
lymphocyte cells as a control group. The highest
apoptotic effect on HL-60 cell lines was observed in
aged garlic extracts at a concentration of 12.5 mg/mL
(10.9%). It was determined that caspase-3 activity in
HL-60 cell lines increased by 1.28 to 3.02 times
compared to lymphocyte cells. It was concluded that
aged garlic extracts triggered apoptosis by increasing
the activity of caspase-3 in HL-60 cell lines. It is
thought that the aging of garlic has an anticancer
effect and additional studies on this subject may bring
new perspectives to cancer treatment.
... This important reactive sulfur compound exerts a broad range of physiological effects through varied mechanisms, including cytotoxic and antitumor activities that are primarily ascribed to its antioxidant properties, reaction with thiol-containing proteins, and great membrane permeability (Borlinghaus et al., 2014;Lee et al., 2013). In cancerous cells, allicin was earlier reported to stimulate cell death and inhibit cell proliferation (Gruhlke et al., 2016); such induction of apoptosis constitutes a crucial contributing mechanism to its anticancer potential (Miron et al., 2008;Oommen et al., 2004). This fascinating thioester from garlic was also proved to restrain the metastasis of colorectal cancer cells by counteracting the formation of new vessels, regulating cell apoptosis, and enhancing immune functions (Chhabria et al., 2015). ...
... This fascinating thioester from garlic was also proved to restrain the metastasis of colorectal cancer cells by counteracting the formation of new vessels, regulating cell apoptosis, and enhancing immune functions (Chhabria et al., 2015). Several studies have similarly documented the role of allicin in promoting apoptosis and preventing cell division of gastrointestinal, pancreatic, liver, cervical, and breast cancers (Chhabria et al., 2015;Hirsch et al., 2000;Oommen et al., 2004;Sun and Wang, 2003;Zhang et al., 2015). More interestingly, a number of synthetic thiosulfinate derivatives with greater in vitro antiproliferative activities than allicin against multidrug-resistant breast cancer cells have been also recently prepared (Roseblade et al., 2017). ...
Allium sativum L. (garlic) has received a growing interest as both a food plant and folk remedy with promising antitumor and chemopreventive potential. So far, a large body of research has been conducted on garlic, mostly focusing on the bulbs, yet its roots remain unstudied and are discarded in considerable amounts as vegetable wastes. Accordingly, for the first time, this study examined the potential of A. sativum roots and their green synthesized silver nanoparticles (AgNPs) against hepatocellular carcinoma (HepG-2), breast cancer (Mcf-7), and colon cancer (Caco-2) cells lines. The formation of AgNPs was confirmed using a Transmission Electron Microscope (TEM), UV‒Visible spectroscopy, and Fourier-Transform Infrared Spectroscopy (FT-IR). Overall, the total ethanolic extract of A. sativum roots (TEEASR) significantly inhibited the growth of Caco-2, Mcf-7, and HepG-2 cells with IC50 values of 2.11 ± 0.03, 21.47 ± 0.15, and 45.12 ± 0.76 µg/mL, respectively, whereas AgNPs exhibited more prominent cytotoxic activity, which in the case of Caco-2 cells, was noticeably greater than doxorubicin (IC50= 0.47 ± 0.04 vs. 2.12 ± 0.04 µg/mL). Additionally, HPLC‒HESI‒HRMS analysis of TEEASR revealed the presence of a variety of metabolites with reported anticancer effects, largely dominated by organosulfur species. Interestingly, the characterized compounds showed moderate to promising binding interactions with the active site of human inositol phosphate multikinase (HIPMK), especially γ-glutamylphenylalanine (6) and allixin (7); highlighting their potential contribution to the notable cytotoxic properties of TEEASR as HIPMK inhibitors. These results might pave the way for the possible therapeutic and pharmaceutical applications of garlic by-products, including the roots, and their biogenic nanoparticles.
... Since now, the presence of several compounds including saponins, sapogenins, flavonoids, thiosulfinates, disulphide, and trisulphide were reported in the Allium genus species. Allium sativum (garlic) is an ancient plant that was used for treating different diseases such as arthritis, heart disease, abdominal growths, diarrhea and worm infestation 14 . The daily consumption of garlic can diminish the cancer risk. ...
... The daily consumption of garlic can diminish the cancer risk. Moreover, its extract can effectively blocked the induced tumors in breast, uterine cervix, skin, and colon 14,15 . Allium hirtifolium Boiss (Persian Shallot) is an Iranian native plant that is usually employed for treatment of rheumatoid, hypertension, inflammation, and healing of wounds 16 . ...
Background: Cervical cancer is one of the major reasons of cancer-related mortality. Human papillomavirus is the most common sexually transmitted viral infection, which can lead to cervical cancer. There is no powerful chemotherapeutic agent for HPV infection and cervical cancer. Some plants have the proper potential to be used for treatment of cervical cancer caused by HPV type 18. Materials and Methods: In this study, cytotoxic effect of extract of four indigenous Iranian plants including Rosa damascene mill, Allium sativum, Allium hirtifolium boiss and Prosopis farcta were investigated on the HeLa cell line. HeLa cells were incubated with different concentrations of extracts and then the cell viability was measured by MTT assay. Results: The viable cell numbers were decreased by increase of the extracts concentration. The Allium sativum showed the higher cytotoxicity in all concentrations than the other ones. Afterwards, Allium hirtifolium Boiss, Rosa damascene mill, and Prosopis farcta showed maximum efficiency to decrease cell viability, respectively. Conclusion: The above four mentioned plants might be used for death of HeLa cell harboring HPV type 18. Therefore, they could be employed as a chemotherapeutic agent in the cervical cancer treatment in future.
... There is evidence that allicin inhibits cancer progression via some mechanisms (102), including cell cycle arrest (80,103), induction of apoptosis (66,67,(103)(104)(105)(106), the histone acetylation induction (107), and the angiogenesis suppression (108). Accordingly, apoptosis induction mediated via allicin has been also displayed on some human colonic cancerous cells (HT-29 and Caco-2 cell lines) (23,67,68). ...
... There is evidence that allicin inhibits cancer progression via some mechanisms (102), including cell cycle arrest (80,103), induction of apoptosis (66,67,(103)(104)(105)(106), the histone acetylation induction (107), and the angiogenesis suppression (108). Accordingly, apoptosis induction mediated via allicin has been also displayed on some human colonic cancerous cells (HT-29 and Caco-2 cell lines) (23,67,68). Also, it was confirmed that incubation of HT-29 cells together with garlic extract enriched by thiosulfinate within 24 h could provoke the apoptosis induction in the cells. ...
Digestive system cancer tumors are one of the major causes of cancer-related fatalities; the vast majority of them are colorectal or gastric malignancies. Epidemiological evidence confirmed that allium-containing food, such as garlic, reduces the risk of developing malignancies. Among all compounds in garlic, allicin has been most researched, as it contains sulfur and produces many second degradation compounds, such as sulfur dioxide, diallyl sulfide (DAS), diallyl trisulfide (DATS), and diallyl disulfide (DADS) in the presence of enzymatic reactions in gastric juice. These substances have shown anti-inflammatory, antidiabetic, antihypertensive, antifungal, antiviral, antibacterial, and anticancer efficacy, including gastrointestinal (GI) cancers, leukemia, and skin cancers. Herein, we summarize the therapeutic potential of allicin in the treatment of GI cancers.
... Traditional medicine has a long history in health maintenance and in disease prevention and treatment. Garlic (A. sativum), which is one of the most studied herbal products, is a plant species that has abundant amounts of phytochemical compounds [4]. Tunceli garlic (Allium tuncelianum) is an endemic type of garlic whose use is becoming more and more common in Turkey. ...
... Su et al. [58] found an increase in the expression of the Caspase 3 gene when they applied garlic extracts to colo205 cells, a human colon cancer cell line. Oommen et al. [4] studied the expression of Caspases 3 and 9 genes and found that it was an antiproliferative effect of garlic and induced apoptosis. In a study by Vemuri et al. [59] a mixture of mash that was prepared with garlic also showed apoptosis in all of the MCF-7, ZR-75 and MDA-MB 231 lung cancer cell lines in the apoptotic markers (Caspase 9 and p53). ...
We aimed to investigate the phytochemical content and pharmaceutical activity of methanol extracts of Allium tuncelianum (MAT). In this study, phytochemical contents of MAT were analyzed by liquid chromatography mass-spectrometry (LC–MS/MS) technique. Anticancer activity was determined on six different cell lines. By flow cytometric method, apoptotic activity was examined with annexin V in human prostate carcinoma (PC3) cell lines where the highest cytotoxic activity was observed. Real Time PCR was used to investigate the molecular genetic size of the effect. Anticholinesterase and antidiabetic activities were performed using enzyme inhibition technique. Enzyme inhibitory activity of MAT was determined using AChE, α-glucosidase enzymes. In these extracts, “μg Analyte/g MAT” as its unit; quinic acid (6458.45 ± 2.389), malic acid (4187.25 ± 0.544) and vanilic acid (349.4 ± 0.052) were found to be major components. The highest cytotoxic activity was found in PC3 cells (IC50: 105.72 µg/mL). Therefore, the mechanism of apoptotic effect in this cell line was also investigated. In a statistically meaningful proportion, MAT increased Caspase 3 and Caspase 9 gene expressions and suppressed IL6, IL8, MMP2 and MMP9 gene expressions. On the other hand, MAT demonstrated effective inhibition effects against AChE (IC50: 11.25 μg/mL), and α-glycosidase (IC50: 9.85 μg/mL) enzymes. As a result, it can be argued that Allium tuncelianum can be used as an alternative treatment for prostate cancer, diabetes and some neurodegenerative diseases.
Graphic abstract
... Allicin compounds present in garlic should be freshly prepared. It was reported earlier that Allicin inhibits cell growth by activating different signaling pathways [95]. Again, it is found that Allicin inhibits the growth of cervical cancer cells by inhibiting NRF2 expression [96]. ...
... Allium species are important vegetables that have been cultivated for thousands of years for use of their taste, aroma, and additionally to treat diseases due to their bactericidal, anticarcinogenic, and hypoglycemic properties (Galmarini 2018, Oommen et al. 2004). Viruses are signi cant causal agents of plant diseases, leading to reduced yields in Allium species. ...
Garlic ( Allium sativum L.), onion ( Allium cepa L.), and leek ( Allium porrum L.) are widely distributed in the Marmara region of Türkiye. Leek yellow stripe virus (LYSV) and Onion yellow dwarf virus (OYDV) are two of the most significant viral pathogens impacting the cultivation of edible Allium plants worldwide, leading to substantial economic losses. To assess the prevalence of these viruses, leaves from onion, garlic, and leek plants were collected from 778 plants across production fields in the Marmara region (Bursa, Edirne, Kocaeli, Kırklareli, Sakarya, and Tekirdağ). Samples were tested for the presence of OYDV and LYSV by ELISA and RT-PCR. Of the samples analyzed, 175 were found positive for OYDV, 79 for LYSV, and 21 showed mixed infection with both viruses. Successful amplification of specific gene regions (NIb-CP for Onion yellow dwarf virus and CP for Leek yellow stripe virus ) was achieved using specific primers. Sequence analysis revealed that the LYSV and OYDV isolates obtained in this study exhibited identities ranging from 84.6–98.1% and 74.1–99.8% with sequences available in GenBank, respectively. Additionally, the reactions of the genotypes to OYDV were also investigated. OYDV isolate TR-OK64 (OR923732) from Bursa was inoculated into 6 garlic and 15 onion genotypes sourced from the Atatürk Horticultural Central Research Institute. Statistical analyses conducted using JMP Pro 13 revealed infected plants' reductions in leaf length, bulb height, bulb width and bulb mass.
... Effects on cholangiocarcinoma (CCA) were investigated by studying allicin, a major organic allyl sulphur component of garlic (Allium sativum) a valued member of amaryllidaceae family. Allicin (10 mg/kg) successfully prevented tumour growth when human liver bile duct carcinoma (HuCCT-1) was implanted into a BALB/c nude mice model of CCA 41 . Results from an in vitro molecular investigation demonstrated that exposure to allicin (20 M) inhibited invasion, HuCCT-1 cell migration, and epithelial-mesenchymal transition (EMT) by decreasing the levels of matrix metalloproteinase (MMP)-2 and -9. ...
Biochemical compounds and substances that are naturally created by organisms are called "natural products", those by plants are "natural phytochemicals", and those with medicinal values are "natural therapeutic phytochemicals". Natural materials were already in medicinal use before the advent of modern technologies made their usage even more widespread. Micromolecules and macromolecules alike have been linked to anti-tumor effects also. Various forms of human cancer can be inhibited or even cured by using natural substances or their derivatives with anti-tumor capabilities. Natural compounds, such as emodin, genistein, gigerol etc., have been extremely important in the history of carcinoma medication for treating human illness. One of the main objectives of natural product research is to discover novel, physiologically active compounds with novel structures and mechanisms of action with no side or inverse effects. The discovery and development of medications to prevent and treat cancer can benefit greatly from natural components.
... S-allyl cysteine, an ingredient in garlic, has been found to prevent the proliferation of human prostate carcinoma cells (Chu et al., 2007). Allicin, another component of garlic, has also been reported to stimulate both caspase-dependent (Oommen et al., 2004) and self-reliant apoptosis in various cancer cells and lessen the toxic effects of chemotherapy. Diallyl sulfides, such as diallyl disulfide (DADS) and diallyl trisulfide (DATS), are produced when allicin is degraded and have been found to promote apoptosis and cell cycle arrest (Park et al., 2005). ...
Garlic cultivation has been done in India since time immemorial and ingested in the Mediterranean and China as a flavour-enhancing spice. Various studies have shown immunomodulatory inducing properties in garlic (Allium sativum), with several proofs showing that it tends to have stimulatory and inhibitory effects on lymphocytes. Certain studies have also demonstrated garlic's therapeutic efficacy enhanced upon separating and eliminating parts causative of inflammatory cytokines. This plant belongs to clade: angiosperms, monocots; order: asparagales; family: liliaceae; subfamily: alliodeae; and genus: allium. The therapeutic effects can be attributed to the volatile oils, sugars, starch, mucilage, albumen, and components enhancing activity. Garlic has several attributes, such as its anti-viral, anti-microbial, anti-cancer, and cardiovascular properties and immunomodulatory effects. The mentioned list does not end as it also has several other uses. This chapter tries to encapsulate some of the pharmacological effects and properties of Allium sativum.
... Effects on cholangiocarcinoma (CCA) were investigated by studying allicin, a major organic allyl sulphur component of garlic (Allium sativum) a valued member of amaryllidaceae family. Allicin (10 mg/kg) successfully prevented tumour growth when human liver bile duct carcinoma (HuCCT-1) was implanted into a BALB/c nude mice model of CCA 41 . Results from an in vitro molecular investigation demonstrated that exposure to allicin (20 M) inhibited invasion, HuCCT-1 cell migration, and epithelial-mesenchymal transition (EMT) by decreasing the levels of matrix metalloproteinase (MMP)-2 and -9. ...
Biochemical compounds and substances that are naturally created by organisms are called "natural products", those by plants are “natural phytochemicals”, and those with medicinal values are “natural therapeutic phytochemicals”. Natural materials were already in medicinal use before the advent of modern technologies making their usage even more widespread. Micromolecules and macromolecules alike have been linked to anti-tumor effects also. Various forms of human cancer can be inhibited or even cured by using natural substances or their derivatives with anti-tumor capabilities. Natural compounds, such as emodin, genistein, gingerol etc., have been extremely important in the history of carcinoma medication for treating human illness. One of the main objectives of natural product research is to discover novel, physiologically active compounds with novel structures and mechanisms of action with no side or inverse effects. The discovery and development of medications to prevent and treat cancer can benefit greatly from natural components.
... Some of the OSCs more commonly studied, as allicin, DADS, or diallyl trisulfide (DATS), have also showed antitumor activity in colon cancer cell lines, including HT-29 [11,[45][46][47]. A similar effect has been described for water-soluble garlic-derivatives, such as S-allylmercaptocysteine. ...
Increasing rates of cancer incidence and the side-effects of current chemotherapeutic treatments have led to the research on novel anticancer products based on dietary compounds. The use of Allium metabolites and extracts has been proposed to reduce the proliferation of tumor cells by several mechanisms. In this study, we have shown the in vitro anti-proliferative and anti-inflammatory effect of two onion-derived metabolites propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO) on several human tumor lines (MCF-7, T-84, A-549, HT-29, Panc-1, Jurkat, PC-3, SW-837, and T1-73). We observed that this effect was related to their ability to induce apoptosis regulated by oxidative stress. In addition, both compounds were also able to reduce the levels of some pro-inflammatory cytokines, such as IL-8, IL-6, and IL-17. Therefore, PTS and PTSO may have a promising role in cancer prevention and/or treatment.
... The high permeability of allicin through cell membranes and rapid reaction with free thiol groups promote its diverse biological and therapeutic functions (8). Allicin is known for its antibacterial, antifungal, and antiparasitic activities (9), as well as its anticarcinogenic (10,11) and anti-inflammatory functions (12,13). Allicin has also been shown to suppress cholesterol biosynthesis by inhibiting squalene monooxygenase and acetyl-CoA synthetase (14). ...
Introduction
Obesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism.
Methods
In the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation.
Results
Allicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in the mean aspect ratio of mitochondria in allicin-treated cells indicate a shift in mitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1).
Discussion
Transcriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings.
... AC is one of the organosulfur compounds in garlic, and various studies have been performed on its role in inducing apoptosis of cancer cells. Studies have shown that AC can induce apoptosis in malignant cells [33,34] through various pathways [34,35] such as caspase-dependent [36] or caspase-independent [37] manner. In addition, apoptosis-inducing factor (AIF) is another agent that causes ACinduced cell death [2]. ...
In this study, chitosan-lecithin nanoparticles modified with polyethylene glycol (PEG) and folic acid (FA) were used to deliver allicin (AC) to colon cancer cells. AC-loaded polyethylene glycol (PEG) and folic acid (FA)-modified chitosan-lecithin nanoparticles (AC-PLCF-NPs) were fabricated via self-assembling procedure. HPLC for AC encapsulation and FA binding, MTT for viability assay, ABTS and DPPH for antioxidant capacity, disc diffusion, MIC and MBC for antibacterial assay, qPCR and AO/PI staining for apoptotic, and CAM assay for angiogenesis effects of AC-PLCF-NPs were used. AC-PLCF-NPs (113.55 nm) were synthesized as single dispersed (PDI: 0.28) and stable (ZP: + 33.18 mV) with 81% AC encapsulation and 48% FA binding. The antioxidant power of AC-PLCF-NPs was confirmed by inhibiting free radicals ABTS (74.25 µg/mL) and DPPH (366.214 µg/mL) and its antibacterial capacity with very high inhibitory effects against gram-negative bacterial strains. MTT results showed higher toxicity of AC-PLCF-NPs (68.06 µg/mL) compared to AC (171.45 µg/mL). Increased expression of caspase 3 and 9 genes showed activation of the intrinsic apoptosis pathway in treated cells, and on the other hand, reduction of vascular and embryonic growth factors in CAM model confirmed the anti-angiogenesis effects of AC-PLCF-NPs. AC-PLCF-NPs can be suggested as a promising therapeutic agent for studies in the field of colon cancer treatment.
... Allicin (45), a diallyl thiosulfinate, presents antineoplastic properties. The activation of CASP3, CASP8 and CASP9 and subsequent induction of apoptosis upon treatment with allicin (45) are observed in the human cervical cancer SiHa cell line [334]. Allicin (45) can induce apoptosis in the colon cancer HCT116 cell line via the mitochondrial-dependent pathway, as it results in an increase in CYCS and apoptosis regulator BAX protein level but a reduction in the expression of the anti-apoptotic protein BCL2. ...
Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.
... Allicin (45), a diallyl thiosulfinate, presents antineoplastic properties. The activation of CASP3, CASP8 and CASP9 and subsequent induction of apoptosis upon treatment with allicin (45) are observed in the human cervical cancer SiHa cell line [334]. Allicin (45) can induce apoptosis in the colon cancer HCT116 cell line via the mitochondrial-dependent pathway, as it results in an increase in CYCS and apoptosis regulator BAX protein level but a reduction in the expression of the anti-apoptotic protein BCL2. ...
Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated
~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted
to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.
... 15 Allicin may induce cell apoptosis, cell cycle arrest and inhibit proliferation. It was seen in a study that allicin can mediate the apoptosis of cancer cells by activating caspase-3, −8 and −9, 16 and also could activate autophagy of human liver cancer cells and induce cell death through apoptosis 15 , 16 It has been confirmed that it does not affect the growth of normal intestinal cells when inducing apoptosis of gastric cancer cells. 17,18 Secondary metabolites of allicin also play antitumor roles by inhibiting tumor cell proliferation and inducing apoptosis 18 ...
Background: Garlic (allium sativum) is given as herbal medicine due to its antimalignanat effect. It has been reported that allium vegetables have marked anticancer effect against stomach and colorectal carcinomas. Organosulfur compounds in garlic activate the metabolizing enzymes and cytochrome P450s to detoxify carcinogens and other foreign compounds like lead. These components act as anticarcinogenic for gastrointestinal tract, lungs and mammary gland in experimental animals. Aim: To evaluate the dose range of garlic (allium sativum) to induce the antitumor effect. Study design: Experimental study Place and duration of study: Department of Anatomy, Shaikh Zayed Postgraduate Medical Institute, Lahore from 1st October 2013 to 31st March 2014. Methodology: Forty five Wistar albino rats of both sexes weighing between 250-350 grams were selected randomly. Two different doses of 500 and 1000 mg/kg of fresh garlic extract were given to the animals by orogastric tube for thirty days. After this period the analysis of quantitative parameters including the diameter of the hepatocytes and hapatic nucleus were recorded and nucleus to cell ratios (N/C Ratios) were calculated. Results: The atrophic changes on the size of hepatocytes and their nucleus is noted in both experimental group B and C as compared to control group A (P<0.001). Conclusion: There is a significant atrophic change, appearance of pyknotic nuclei indicating the apoptosis. That is leading to decrease in N/C ratio, beneficial in producing the anticarcinigen effect. Keywords: Garlic (allium sativum), hepatocytes, atrophy, pyknotic nuclei, albino rats
... Ethanol, methanol, acetone, and ethyl acetate extracts of onion were evaluated for their antibacterial activity against 15 bacterial strains, the results showed that the ethyl acetate extract had higher bactericidal effect due to the presence of high concentration of phenolic compounds (Mahomoodally et al., 2018). Many studies have shown that organic sulfur compounds provide the antimicrobial effect of Allium species, such as such as diallyl trisulfide (DTS), diallyl disulfide (DDS) in garlic (Oommen et al., 2004;El-Sayed et al., 2017a). Chinese chive share a common sulfur biochemistry as garlic and onion. ...
Chinese chive ( Allium tuberosum Rottler) is a popular food from Allium species in East and Southeast Asia. Most Allium species possess characteristic aromas and have antimicrobial activity. In this study, the antimicrobial activities of root, leaf, and scape extracts of Chinese chive at different pH levels (3.0, 5.0, 7.0, 9.0, and 10.7) were compared. The most pronounced activity was produced by the scape extract, and the greatest activity was obtained at pH 5.0. HPLC and GC–MS analysis showed that the major active ingredient was 2-amino-5-methylbenzoic acid. The mechanism of action of Chinese chive scape extracts may involve the depression or disruption of cell membrane integrity, according to our results of the leakage of electrolytes and protein, as well as scanning electron microscopy and transmission electron microscopy observations.
... Produtos Naturais e a Apoptose: Produtos Naturais e a Apoptose: Produtos Naturais e a Apoptose: Produtos Naturais e a Apoptose: Produtos Naturais e a Apoptose: Um Enfoque Promissor para a Um Enfoque Promissor para a Um Enfoque Promissor para a Um Enfoque Promissor para a Um Enfoque Promissor para a Paclitaxel R e f e r ê n c i a R e f e r ê n c i a R e f e r ê n c i a R e f e r ê n c i a R e f e r ê n c i a Caspases T T T T Tabela 1 -abela 1 -abela 1 -abela 1abela 1 -Produtos naturais e seus respectivos alvos celulares em mecanismos de apoptose OOMMEN et al., 2004LU et al., 2004CHAKRABARTY et al., 2002HUANG et al., 2004MIYOSHI et al., 2003KEUM et al., 2002ZHANG et al., 2004LEUNG et al., 2005FERNANDES et al., 2005SCHROETER et al., 2001SCHROETER et al., 2001CHAN et al., 2003KITADA et al., 2003KITADA et al., 2003HUANG, 2001 DIRSCH;GERBES;VOLLMAR,1998 CHIU;WAN, 1999 ZHOU;ZHU, 2003 Bcl-2 No passado, o desenvolvimento de novas drogas para o tratamento das doenças que mais acometem o homem era dificultado pelo pouco conhecimento que se tinha sobre os fenômenos envolvidos nos diversos processos patológicos. Com os crescentes avanços da imunologia, biologia molecular, genética, fisiologia básica e modelagem molecular, vários alvos terapêuticos vêm sendo descritos, propiciando o crescimento de outras áreas como a farmacologia e, consequentemente, a terapêutica. ...
A morte celular programada, denominada apoptose celular, faz parte de diversos processos vitais, dentre os quais podemos citar o desenvolvimento embrionário, o controle de tumores e a regulação de populações de células do sistema imune. Distúrbios na regulação da apoptose estão envolvidos em uma variedade de doenças, tais como a Síndrome da Imunodeficiência Adquirida (AIDS), o câncer, a doença de Alzheimer, o mal de Parkinson e as doenças auto-imunes. Hoje há acesso a estudos bastante aprofundados sobre moléculas que atuam diretamente em alvos terapêuticos nos mecanismos apoptóticos e que, por esta razão, poderiam ser utilizadas no tratamento de várias doenças ainda sem cura. Os trabalhos mais promissores nesta área focalizam, por exemplo, substâncias isoladas do alho (Allium sativum), terpenos de Caseria membranaceae e de Zingiber mioga, além de alguns produtos do ácido gambógico, isolado de Garcinia hurburyi. Muitos esforços têm sido empregados visando aplicar moléculas capazes de induzir a apoptose no tratamento do câncer, entretanto são poucos os trabalhos direcionados a outras doenças. Esta revisão tem como objetivo principal mostrar o potencial de moléculas de origem natural para o tratamento do câncer e dessas outras patologias, com base nos mais conhecidos alvos terapêuticos envolvidos na apoptose.
... these results are consistent with those of previous studies. 30,35,36 Recently, it has been shown that the PGC-1α and AMPK-SIRT1 pathways are associated with the regulation of energy metabolism and mitochondrial biogenesis. 15 The link between the AMPK/SIRT1/ PGC1α signaling pathway and ovarian cancer is yet to be studied. ...
Platinum-based chemotherapy promotes drug resistance in ovarian cancer. We investigated the anti-chemoresistance characteristics of diallyl trisulfide (DATS) in cisplatin-resistant ovarian cancer cells, in vitro and in vivo. Previous preclinical studies have revealed that DATS regulates distinct hallmark cancer-signaling pathways. The cell cycle pathway is the most investigated signaling pathway in DATS. Additionally, post-DATS treatment has been found to promote proapoptotic capacity through the regulation of intrinsic and extrinsic apoptotic pathway components. In the present study, we found that treating cisplatin-sensitive and cisplatin-resistant ovarian cell lines with DATS inhibited their proliferation and reduced their IC50. It induced cell apoptosis and promoted oxidative phosphorylation through the regulation of the AMPK/SIRT1/PGC1α pathway, OXPHOS, and enhanced chemotherapy sensitivity. DATS treatment alleviated glutamine consumption in cisplatin-resistant cells. Our findings highlight the role of DATS in overcoming drug resistance in ovarian cancer in vitro and in vivo. In addition, we elucidated the role of the AMPK/SIRT1/PGC1α signaling pathway as a potential target for the treatment of drug-resistant ovarian cancer.
... Numerous health benefits have been ascribed to organosulfur compounds, including its immunomodulatory properties in cancer [9,[119][120][121]. A report in the literature noted an association between garlic consumption and decreased incidence of distal colon cancer in women in a cohort study [120]. ...
The benefits of garlic to health have been proclaimed for centuries; however, only recently have Allium sativum and its derivatives been proposed as promising candidates for maintaining the homeostasis of the immune system. The complex biochemistry of garlic makes it possible for variations in processing to yield different preparations with differences in final composition and compound proportion. In this review, we assess the most recent experimental results, which indicate that garlic appears to enhance the functioning of the immune system by stimulating certain cell types, such as macrophages, lymphocytes, natural killer (NK) cells, dendritic cells, and eosinophils, by mechanisms including modulation of cytokine secretion, immunoglobulin production, phagocytosis, and macrophage activation. Finally, because immune dysfunction plays an important role in the development and progress of several diseases, we critically examined immunoregulation by garlic extracts and compounds isolated, which can contribute to the treatment and prevention of pathologies such as obesity, metabolic syndrome, cardiovascular disorders, gastric ulcer, and even cancer. We concluded that A. sativum modulates cytokine secretion and that such modulation may provide a mechanism of action for many of their therapeutic effects.
... Sulphur substances are typically related to the organoleptic properties of the cabbage family and also of vegetables of the Allium genus, as onion, garlic and leek (Poojary et al. 2017). Many of them, as ajoene and allicin, are bacteriostatic agents besides having anticarcinogenic and antiinflammatory activities (Oommen et al. 2004;Dirsch et al. 1998). Nitrogenous compounds are mainly alkaloids, which usually present very high bioactivity even in low concentrations. ...
In the past, research and development in food drying had focused on the processes as much as on the products. The technology was aimed to extend the food shelf-life without paying due attention to retaining quality attributes. However, recently, considerable efforts have been made to study and develop dehydrated products with higher nutritional quality. In this regard, the concept of functional food appeared to describe the potential of foods to improve human health by providing essential nutrients as carbohydrates, lipids, proteins, and other substances present in small amount as vitamins, minerals and bioactive compounds, with a large variety of health benefits. This chapter has the purpose of finding the impact of drying processes on bioactives in foods. After conducting an extensive literature review, a conclusion has been drawn on that the interaction of factors during drying, the bioactives extraction procedures and the nature of the food matrix finally determine retention. Beyond the nutritional topic, organoleptic and economic parameters must be considered in applied research for the selection of a drying method, adding complexity to the practice. By combining experiments and mathematical simulation that considers all coupled factors acting simultaneously, the science and technology of bioactives, and their retention will improve from the present state of affairs.KeywordsCarotenoidsPhenolic compoundsVitamin CVitamin E
... An early study in 1960 showed that tumor growth could be inhibited by intraperitoneal injection of tumor cells into mice after culturing ascites with allicin in vitro (Dipaolo and Carruthers, 1960). Allicin can induce cancer cells to form apoptotic bodies and DNA ladders (Oommen et al., 2004). Furthermore, it has been found that allicin can induce redox shifts in cultured human cells, which results in the activation of the mitochondrial apoptotic pathway (Miron et al., 2008). ...
Allicin is the main active ingredient in freshly-crushed garlic and some other allium plants, and its anticancer effect on cancers of digestive system has been confirmed in many studies. The aim of this review is to summarize epidemiological studies and in vitro and in vivo investigations on the anticancer effects of allicin and its secondary metabolites, as well as their biological functions. In epidemiological studies of esophageal cancer, liver cancer, pancreatic cancer, and biliary tract cancer, the anticancer effect of garlic has been confirmed consistently. However, the results obtained from epidemiological studies in gastric cancer and colon cancer are inconsistent. In vitro studies demonstrated that allicin and its secondary metabolites play an antitumor role by inhibiting tumor cell proliferation, inducing apoptosis, controlling tumor invasion and metastasis, decreasing angiogenesis, suppressing Helicobacter pylori, enhancing the efficacy of chemotherapeutic drugs, and reducing the damage caused by chemotherapeutic drugs. In vivo studies further demonstrate that allicin and its secondary metabolites inhibit cancers of the digestive system. This review describes the mechanisms against cancers of digestive system and therapeutic potential of allicin and its secondary metabolites.
... However, in the latter study, it is not clear how apoptosis was detected, and no molecular mechanism was investigated [85] (Table 1). Starting at lower concentrations, the intrinsic pathway has been activated also on oral tongue squamous cell carcinoma Tca-8113 and SCC-25 [12 µg/mL (73.9 µM); 48 h] [86], luminal A (MCF7; 40 µM; 24 h) and triple-negative (HCC-70; 20 µM; 24 h) breast carcinomas [87], murine fibrosarcoma L929, SW480 (50 µM, 24 h) [88] or Siha (50 nM; 72 h) [16], gastric cancer HGC27 and AGS [10 µg/mL (61,61 µM); 48 h] [89], colorectal cancer Caco-2, HT29 (500-1000 µM) [2,90,91], and HCT116 (25 µM; 48 h) [13,14], lymphoma EL-4 (4 µg/mL (24.6 µM); 24 h) [13,92] and L5178Y (1, 09 mM; treatment time not specified) [4], leukemia HL-60 (5 µM; 16 h) and U937 (20 µM; 16 h) ( Table 1) [2]. ...
Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.
... AL inhibited the growth of cancer cells of both murine and human origin. Besides, AL induced the production of apoptotic bodies, nuclear condensation and a typical DNA ladder found in cancer cells (Oommen et al., 2004). ...
... There are numerous anticancer phytochemicals, including fatty acids, vitamins, antioxidant phenolic, dietary fiber, flavonoids, polyphenols etc. Herein, we focus on garlic compounds, the phytochemicals with a num-ber of beneficial pro-health effects (i.e., anticancer, antifungal, antimicrobial, antithrombotic, supporting cardiovascular disease treatment, stimulating the immune system, etc.) [5,6]. Garlic active compounds (organosulfur compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), diallyl thiosulfonate (allicin), E/Zajoene, S-allyl-cysteine (SAC) or S-allyl-cysteine sulfoxide (alliin), among others) inhibit cancer cell growth [7], and induce caspase-dependent [8] and independent [9] apoptosis in different cancer cell lines. Additionally, some chemicals mentioned above (e.g., DADS, DATS, SAC) are well-known as sulfane sulfur precursors [10][11][12]. ...
Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are garlic oil compounds exhibiting beneficial healthy properties including anticancer action. However, these compounds are sparingly water-soluble with a limited stability that may imply damage to blood vessels or cells after administration. Thus, their encapsulation in the oil-core nanocapsules based on a derivative of hyaluronic acid was investigated here as a way of protecting against oxidation and undesired interactions with blood and digestive track components. The nuclear magnetic resonance (1H NMR) technique was used to follow the oxidation processes. It was proved that the shell of the capsule acts as a barrier limiting the sulfur oxidation, enhancing the stability of C=C bonds in DADS and DATS. Moreover, it was shown that the encapsulation inhibited the lysis of the red blood cell membrane (mainly for DADS) and interactions with serum or digestive track components. Importantly, the biological functions and anticancer activity of DADS and DATS were preserved after encapsulation. Additionally, the nanocapsule formulations affected the migration of neoplastic cells—a desirable preliminary observation concerning the inhibition of migration. The proposed route of administration of these garlic extract components would enable reaching their higher concentrations in blood, longer circulation in a bloodstream, and thus, imply a better therapeutic effect.
This work presents the results of field research conducted in 2023-2024 in the Czudec commune (Podkarpackie voivodeship). The aim of the study was to analyze the species composition of herbaceous plant flora at selected sites, with particular emphasis on medicinal species, and to indicate the places of their greatest concentration for the purpose of obtaining them from the natural state.
During the research, a herbarium and a systematic floristic list were prepared, which included 286 species of herbaceous plants belonging to 45 plant families. The analysis of available literature and internet data allowed to determine that 158 recorded species have medicinal properties and are used in conventional and/or unconventional or folk medicine.
It has been widely accepted that plants possess inherent biological potential, fiber, and phenolic content, which collectively mount up to health promotion. Globally, the bioactive compounds of medicinal and therapeutic plants are an inestimable asset in the struggle against severe diseases. Antibiotics have been employed to treat microbial infections and these bioactive agents with low molecular weight have been found pertinent in various medicinal contexts. Abusive and excessive use of antibiotics over the last few decades has spur the proliferation of microbe’s resistant to antibiotics, making medication treatments ineffectual. As an excellent source of antimicrobial compounds with potential applications, plants can supplement or alter antibiotics. Many secondary metabolites of different classes like terpenes, polyphenols, and alkaloids have been shown to showcase antimicrobial properties. Moreover, antimicrobial resistance (AMR) occurs when bacteria, viruses, fungi, and parasites deplete their responsiveness to antimicrobial medicines. The use of phytomolecules or natural products from medicinal plants as an alternative to antibiotics in combating microbial infections has gained attention due to the increasing concerns related to antibiotic resistance in microbes. The current state of knowledge regarding the utilization and therapeutic applications of naturally occurring bioactive is the subject of this chapter.
Objectives: We investigated the effects of allicin on nasal mucosa via an experimental study. Methods: In the study, 16 male New Zealand Albino (2.5-4.5 kg) rabbits were used. The right nasal passages of the 8 rabbits were included in the control group (Group 1, n = 8), and the right nasal passages of the 8 different rabbits were included in the study group (Group 2, n = 8). In the study group (Group 2), a Merocel tampon soaked in Allicin (Alli Tech; Dulwich Health) (0.5 mg/kg). In the control group (Group 1), a Merocel tampon soaked in serum physiologic was placed in the right nasal passage for 3 days (first to third days of the study). On the fourth day, nasal mucosa was excised and histopathological examinations were performed. Results: Our results showed that there were no significant differences in terms of bleeding, congestion, inflammation, calcification, and seromucous gland density between the study and control groups (P > .05). In light microscopic evaluation, moderate density of lymphocytic cells beneath the surface epithelium and, further down, seromucous gland structures, dense seromucous glands, and occasional ductal structures were observed in the study group. Congested vascular structures beneath the respiratory epithelium and adjacent to a thick-walled vascular structure, coarse calcification is observed in the control group. Conclusion: It has been demonstrated that the Allicin-soaked Merocel pack does not have adverse effects on rabbit nasal mucosa, and it does not lead to mucosal bleeding, congestion, inflammation, and calcification, and changes in the seromucous gland density. Considering the antibacterial and antiviral effects of allicin, it is appropriate to plan research in humans to evaluate its use in nasal packs applied during epistaxis, septoplasty, rhinoplasty, and endoscopic sinus surgery.
Objective: Garlic can help humans ensure healthy lives and promote well-being for all at all ages by sufficient zinc and magnesium intake.Method: Serpentine treated it by microwaving and sintering to enhance its crystallinity as well as its magnesium and zinc ion release rates. Furthermore, an enriched garlic enzyme extract had an approximately 8-fold increase in alliinase activity.Results: Strong bonding was observed for the microwaved and sintered powders, but also facilitated zinc ion reactions and reduced lattice defects. Accordingly, used for the garlic growth and enzyme experiments.Conclusions: (1) The sintered powder excellent magnesium and zinc ion release capability. (2) The enriched garlic enzymes had high alliinase activity, likely increasing the health benefits of the garlic.
Background
The activated oncogenic Notch signalling is an emerging target to treat cancer progression and recurrence. Synthetic inhibitors of Notch receptors are in pre-clinical studies. However, the overexpression of Notch signalling molecules at the gene level needs to be regulated to control cancer progression.
Objective
We propose that this can be achieved by gene-regulatory drugs in combination with natural phytochemical compounds.
Methods
The ethanol extract of Allium sativum alone and in combination with DAPT and ATRA were evaluated for cytotoxicity on A549 cells by MTT and Trypan blue assays. Their effects on Notch 1, Hes 1 and p53 gene expressions were studied by RT-PCR and qPCR. Their inhibition on metastatic invasion of A549 cells was analyzed by in vitro wound scratch assay. The phytochemicals of the extract were identified by GC-MS analysis.
Results
Many organosulfur compounds having anti-cancer potency were identified in GC-MS. The combination treatment with 50µg (IC50) of garlic extract exhibited a highly significant (P≤0.01) synergistic inhibitory effect on A549 cell growth and migration. It has also significantly reduced the expression of Notch 1 and Hes 1 oncogenes and enhanced p53 gene expression, compared with the individual treatments. This indicates the synergistic action of the extract on the downregulation of Notch signalling at the mRNA level.
Conclusion
Our study results imply that the combination therapies have potent molecular treatment action via down-regulating Notch signaling target genes and upregulating p53 gene expression as an underlying mechanism of inhibitory action on A549 lung cancer cells.
Introdução: Os riscos de interações entre produtos naturais e alopáticos são consideravelmente altos e alarmantes. Por serem de origem natural, são considerados pela maior parte da população como seguras e isentas de toxicidade. É difícil estabelecer a origem de uma interação entre plantas medicinais, fitoterápicos e medicamentos alopáticos, especialmente em pacientes poli medicados, pois muitos compostos químicos presentes nas plantas não possuem seus mecanismos de ação conhecidos. Também deve-se ressaltar que as plantas medicinais possuem mais de um composto ativo, o que aumenta a probabilidade de ocorrência de interações medicamentosas, diante disso, o objetivo deste trabalho foi o de realizar um levantamento de informações existentes na literatura sobre a interação entre alopáticos e fitoterápicos com anticoagulantes. Metodologia: Estudo de revisão bibliográfica, com finalidade integrativa. Resultado: A varfarina e a heparina são medicamentos, e existem várias outras plantas, que apresentam como metabólito secundário as cumarinas, que inibem ou ativam inúmeras enzimas e, quando administradas com anticoagulantes, aumentam o risco de sangramentos. Essa interação ocorre devido à constituição muito complexa das plantas e dos fitoterápicos, ou seja, com muitos compostos químicos que são responsáveis pelas interações com efeito aditivo, antagônico ou sinérgico. Conclusão: Conforme a revisão de literatura, observou se que uso da varfarina e da heparina com interação com tratamentos alopáticos e fitoterápicos tem benefícios e malefícios, se não utilizados corretamente. No entanto, o uso destes fármacos com interação de plantas medicinais (chá verde, boldo, camomila e alho) podem causar sangramentos com potencial hemorrágicos.
Bawang putih berasal dari daerah tropis dan subtropis di Asia Tengah dan menyebar ke bagian lain dunia melalui perdagangan dan kolonisasi. Bawang putih memiliki sifat farmasi yang tinggi dengan adanya lebih dari 33 senyawa komponen bioaktif mengandung belerang yang ampuh menghambat pertumbuhan bakteri, virus, dan jamur. Kandungan utama dalam umbi bawang putih adalah senyawa allicin yang mengandung sulfur (thio-2-propene-1-sulfinic acid S-allyl ester). Allicin diketahui memiliki berbagai fungsi biokimia, seperti antikoagulan, antihipertensi, antimikotik, antitumor, antioksidan, antipenuaan, detoksifikasi logam berat, fibrinolusis, hipolipidemik (penurun lemak) dan penguat sistem imun. Program pemuliaan tanaman yang menargetkan kultivar bawang putih dengan kandungan allicin lebih tinggi terus diupayakan oleh para ilmuwan untuk meningkatkan manfaatnya. Program ini dilakukan dengan pendekatan rekayasagenetika dan rekayasa jalur biosintesis dari senyawa penyusun allicin. Kajian molekuler tentang biosintesis, transportasi, dan regulasi senyawa allicin pada bawang putih dalam reviu ini tidak hanya memberikan wawasan tentang pengetahuan dasar kita, tetapi juga memfasilitasi rekayasa metabolisme bawang putih di masa depan menggunakan teknologi transgenik dan rekayasa genetika.
Intensive Chemical and pharmacological investiagtion of species Allium is conducted by Italien, French, English,American, Indian, Chinese and Japonaise scientists during the last years. The medicinal drugs with anticancer, antimicrobal, anti atherosclerosis activity. Taking into account the above mentioned, it is perspective to continue the study of species Allium grown in Georgia to receive the medicinal drugs with high therapeutic effect.
Background - According to National Institute for Health and Care Excellence quality standards, the assessment of fall risk and preventing falls should be multifactorial and include self-reported questions like fall history, fear of falling (FoF), self-perception of functional ability, environment hazards, gait pattern, balance, mobility and muscle strength. Concerning the self-reported data, some studies described subjectivity and difficulty in extracting reliable information when using such methods. History and number of previous falls are often used as golden standard in fall risk assessment studies; however, these questions are source of misjudgement, in part, due to difficulty for an older person remember exactly how many times he/she had fallen in a past period of time. Objective - The study aimed to compare self-reported questions and standard and validated measures for screening risk of fall to verify the confidence of the self-reported data. Methods - 506 community-dwelling adults aged 50+ years old (mean age 69.56 ± 10.29 years old; 71.7% female) were surveyed regarding demographics, history of fall, FoF, sedentary lifestyle, use of upper extremities to stand up from a chair, by self-reported questionnaire; analysis of gait, balance and muscle strength, by standard and validated measures for screening risk of fall - 10 meters walking speed test, Timed Up & Go test and 30 second sit to stand test, respectively. Independent samples t tests were performed to compare groups. Results - 33.2% of the sample reported at least one fall in the last year (fallers), 50% reported FoF, 46.4% sedentary lifestyle, 31.8% needed their upper extremities assistance to stand from a chair. Fallers demonstrated lower scores of gait velocity (p < 0.001), lower extremities strength (p < 0.001) and balance (p = 0.034) compared with nonfallers; who reported sedentary lifestyle also showed lower scores of gait velocity (p < 0.001), lower extremities strength (p = 0.001) and balance (p < 0.001) compared with non-sedentary. Simultaneously, who assumed FoF showed lower scores of gait velocity (p < 0.001), lower extremities strength (p < 0.001) and balance (p < 0.001) compared with who had no FoF. Finally, those who use the upper extremities to stand up from a chair showed lower scores of gait velocity (p < 0.001), lower extremities strength (p < 0.001) and balance (p < 0.001) compared with those who do not. Conclusions - The findings suggest that self-reported data like history of falls, sedentary lifestyle, FoF and use of upper extremities to stand up from a chair, obtained by simple questions, have emerged as reliable information on risk factors for falling and can be used to complete the fall risk screening.
Glioma is one of the most common malignancies of the central nervous system. Due to inadequate response to the current treatments available, glioma has been at the center of recent cancer studies searching for novel treatment strategies. This has prompted an intensive search using linkage studies and preliminary evidence to gain efficient insight into the mechanisms involved in the alleviation of the pathogenesis of glioma mediated by miRNAs, a group of noncoding RNAs that affect gene expression posttranscriptionally. Dysregulated expression of miRNAs can exacerbate the malignant features of tumor cells in glioma and other cancers. Natural products can exert anticancer effects on glioma cells by stimulating the expression levels of tumor suppressor miRNAs and repressing the expression levels of oncogenic miRNAs. In this review, we aimed to collect and analyze the literature addressing the roles of natural products in the treatment of glioma, with an emphasis on their involvement in the regulation of miRNAs.
Objective
To determine the effect of Zanthoxylum piperitum extracet (ZPE) on apoptosis and analyze anticancer substances in ZPE, changes in proteins related to apoptosis, and pathological changes in tumors in mouse.Methods
Fifteen 4-week-old female BALB/c nu/nu mice were divided into 3 groups depending on ZPE dose, with 5 in each group. AGS gastric carcinoma cells (1 × 106 cells/200 µL) were subcutaneously injected into the flank of each mouse. One week after the injection of AGS cells, ZPE was administered to the skin tissue [10 or 50 mg/(kg·d)] in the low- and high-dose groups, respectively for 20 days. Control animals were injected with vehicle only. After 3 weeks, the tumor was extracted and carried out for immunohistochemistry, the tendency of apoptosis and p53 in the body was checked using TdT-mediated dUTP nick-end labeling (TUNEL) assay. For 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V dead cell staining, cell cycle arrest and Western blotting, AGS gastric carcinoma cells were incubated with various concentrations of ZPE for 24 h. Cell survival rates were analyzed by MTT assays. Apoptosis was analyzed using annexin V dead cell staining and cell cycle arrest and measured using Muse cell analyzer.ResultsHigh performance liquid chromatography (HPLC) analysis showed that ZPE contained organic sulfur compounds such as alliin and S-allylcysteine. MTT assay results revealed that ZPE (10–85 µ g/mL) could effectively inhibit the growth of AGS gastric cancer cells at higher concentrations (P<0.05, P<0.01). The annexin V & dead cell staining assay and cell cycle arrest assay confirmed a dose-dependent increase in the apoptosis rate and G1 phase in ZPE (10–70 µ g/mL) groups. ZPE decreased the expression of anti-apoptotic proteins (p-Akt, p-MDM2, Bcl-2), while increased pro-apoptotic proteins (cleaved PARP, p53, pro-Caspase 3, Bax). TUNEL assays revealed an increase in cell apoptosis. Immunohistochemistry staining confirmed the involvement of p53.ConclusionZPE decreases AGS cell proliferation and induces apoptosis by inhibiting Akt and MDM2 expression.
To determine the in vitro efficacy of indigenous plants on the inhibition of development of eggs of Ascaridia galli, a study was carried out in the laboratory of Department of Parasitology from January to May, 2012. Leaves of five plants namely pineapple (Ananas comosus), turmeric (Curcuma domestica), akanda (Calotropis gigantea), garlic (Allium sativum) and custard apple (Annona reticulata) were selected. Two different types of preparation such as fresh juice and dust material were used. Fresh leaves juice at 5%, 10% and 20% concentration and dust of leaves at 5%, 10% and 20% concentration were used for screening. Among the selected plants in all three concentrations of fresh juice of leaves, pineapple was the highest effective plant (86.9%) at 20% concentration followed by pineapple at 10% concentration (84.0%), garlic at 5% concentration (81.8%), turmeric at 20% concentration (78.9%), pineapple at 5% concentration (78.9%), turmeric at 10% concentration (73.9%), garlic at 10% concentration (73.0%). Among the plants in all concentrations of dust of leaves, pineapple at 20% concentration (76.9%) was observed as the best plant followed by akanda at 5% concentration (75.0%) and turmeric at 20% concentration (73.3%). The present study suggests that pineapple, turmeric and garlic leaves are effective and can be used against the development of eggs of A. galli. So, further studies are required to determine the side effects of these plants and determine the recommended doses in poultry.
Epidemiological studies link increased garlic (Allium sativum) con- sumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds ex- hibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their ef- fects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well- established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompa- nied by induction of jun kinase activity and a marked increase in endog- enous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhib- itory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.
Release of cytochrome c is important in many forms of apoptosis. Recent studies of CD95 (Fas/APO-1)-induced apoptosis have implicated caspase-8 cleavage
of Bid, a BH3 domain-containing proapoptotic member of the Bcl-2 family, in this release. We now demonstrate that both receptor-induced
(CD95 and tumor necrosis factor) and chemical-induced apoptosis result in a similar time-dependent activation of caspases-3,
-7, -8, and -9 in Jurkat T cells and human leukemic U937 cells. In receptor-mediated apoptosis, the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp
fluoromethyl ketone (Z-VAD.FMK), inhibits apoptosis prior to commitment to cell death by inhibiting the upstream activator
caspase-8, cleavage of Bid, release of mitochondrial cytochrome c, processing of effector caspases, loss of mitochondrial membrane potential, and externalization of phosphatidylserine. However,
Z-VAD.FMK inhibits chemical-induced apoptosis at a stage after commitment to cell death by inhibiting the initiator caspase-9
and the resultant postmitochondrial activation of effector caspases. Cleavage of Bid but not release of cytochromec is blocked by Z-VAD.FMK demonstrating that in chemical-induced apoptosis cytochrome c release is caspase-independent and is not mediated by activation of Bid. We propose that caspases form an integral part of
the cell death-inducing mechanism in receptor-mediated apoptosis, whereas in chemical-induced apoptosis they act solely as
executioners of apoptosis.
Garlic has been used in herbal medicine for thousands of years. While garlic oil contains many components and has been widely studied, the pharmacology of pure allicin, a constituent of garlic oil, is not well understood. We report that allicin inhibits human platelet aggregation in vitro without affecting cyclooxygenase or thromboxane synthase activity or cyclic adenosine monophosphate (AMP) levels. Allicin does not alter the activity of vascular prostacyclin synthase. However, it inhibits ionophore A23187-stimulated human neutrophil lysosomal enzyme release. In vivo allicin dilates the mesenteric circulation of the cat independent of prostaglandin release or a beta adrenergic mechanism.
Apoptosis is a morphologically distinct form of programmed cell death that plays a major role during development, homeostasis,
and in many diseases including cancer, acquired immunodeficiency syndrome, and neurodegenerative disorders. Apoptosis occurs
through the activation of a cell-intrinsic suicide program. The basic machinery to carry out apoptosis appears to be present
in essentially all mammalian cells at all times, but the activation of the suicide program is regulated by many different
signals that originate from both the intracellular and the extracellular milieu. Genetic studies in the nematode Caenorhabditis
elegans and in the fruit fly Drosophila melanogaster have led to the isolation of genes that are specifically required for
the induction of programmed cell death. At least some components of the apoptotic program have been conserved among worms,
insects, and vertebrates.
Allicin (diallyl thiosulfinate) is the main biologically active component of the freshly crushed garlic extracts. In the present work the ability of allicin to cross through membranes (artificial and biological) was studied. Partition coefficients of allicin in water/octanol, water/hexadecane and water/phospholipids mixtures were determined. Using phospholipid vesicles loaded with hydrophilic thiols (reduced glutathione or 2-nitro-5-thiobenzoate), we observed that allicin freely permeates through phospholipid bilayers and interacts with the SH groups. The reaction rate of allicin with SH containing molecules after crossing the membrane was the same as in solution. Fast diffusion and permeation of allicin across human red blood cell membranes was also demonstrated. Allicin does not induce leakage, fusion or aggregation of membrane. The high permeability of allicin through membranes may greatly enhance the intracellular interaction with thiols.
Curcumin (diferuloyl methane), the yellow pigment in turmeric (Curcuma longa), is a potent chemopreventive agent. Curcumin induces apoptosis of several, but not all, cancer cells. Many cancer cells protect themselves against apoptosis by activating nuclear factor-kappaB (NF-kappaB)/Rel, a transcription factor that helps in cell survival. Signal-induced activation of NF-kappaB is known to be inhibited by curcumin. To understand the role of NF-kappaB in curcumin-induced apoptosis, we stably transfected relA gene encoding the p65/RelA subunit of NF-kappaB, into l-929 cells (mouse fibrosarcoma) and the relA-transfected cells were resistant to varying doses of curcumin (10(-6)-10(-4) m), whereas the parental cells underwent apoptosis in a time- and dose-dependent manner. The relA-transfected cells showed constitutive NF-kappaB DNA binding activity that could not be inhibited by curcumin and did not show nuclear condensation and DNA fragmentation upon treatment with curcumin. When a super-repressor form of IkappaB-alpha (known to inhibit NF-kappaB) was transfected transiently into relA-transfected cells, the cells were no longer resistant to curcumin. Our results highlight a critical anti-apoptotic role for NF-kappaB in curcumin-induced apoptosis.
Allyl sulfur compounds play a major role in the chemoprevention against carcinogenesis. The present study compared the antiproliferative effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and garlic extract on p53-wild type H460 and p53-null type H1299 non small cell lung cancer cells (NSCLC). The DAS and DADS treatment of both H460 and H1299 cells resulted in the highest numbers of cells in apoptotic state as measured by acridine orange staining, however, garlic extract treatment did not induce any significant apoptotic cells by MTT assay. DADS was found to be more effective in inducing apoptosis on NSCLC. The level of p53 protein in H460 cell was increased following DADS treatment. DAS and garlic extract treatment of H460 cells induced a rise in the level of Bax and a fall of Bcl-2 level. These results demonstrate that DAS, DADS and garlic extract are effective in reduction of anti-proliferative gene in NSCLC and suggest that modulation of apoptosis-associated cellular proteins by DAS, DADS and garlic extract may be the mechanism for apoptosis which merit further investigation as potential chemoprevention agents.
An extensive and expanding information base that incorporates data from epidemiologic, animal, and laboratory investigations
documents the relation between garlic consumption and decreased risk of developing cancer at various organ sites (1–3). Garlic and other allium-related plants contain alliin, an allylsulfinothiolated derivative of cysteine, that is transformed
exogenously into a number of mono-, di-, and triallylsulfinyl analogues when the bulb is crushed, minced, or damaged (5). These bioactive compounds interact with a number of molecular targets whose functions range from control of cell cycle
to expression of crucial antioxidant and detoxification enzymes (6–8). Modulation of each of these processes may underlie garlic’s putative anticancer potential.
The reputation of garlic as an effective remedy for tumours extends back to the Egyptian Codex Ebers of 1550 BC. Several garlic compounds, including allicin and its corresponding sulfide, inhibit the proliferation of several human malignant cells. Ajoene is a garlic-derived compound produced most efficiently from pure allicin and has the advantage of a greater chemical stability than allicin. Recently, ajoene was shown to inhibit proliferation and induce apoptosis of human leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM-I. More significantly, ajoene was shown to induce 30% apoptosis in myeloblasts from a chronic myeloid leukaemia patient in blastic crisis. Acute myeloid leukaemia (AML) is a heterogeneous malignant disease in which disease progression at the level of CD34-positive cells has a major impact on resistance to chemotherapy and relapse.
The aim of the present study was to investigate the effect of ajoene on changes in the expression of apoptosis-related proteins: bcl-2 and caspase-3, induced by two principal drugs used in treatment of AML, cytarabine and fludarabine, in KGI human myeloid leukaemia CD34-positive-resistant cells. Both quantitative ELISA measurement of bcl-2 and colourimetric measurement of active caspase-3 were used.
Quantitative ELISA measurement of bcl-2 (units per million cells) showed treatment of KG1-resistant leukaemia cells with 40 microM ajoene alone to significantly reduce the bcl-2-expression from 239.5 +/- 1.5 in control cultures to only 22.0 +/- 4.0 in ajoene-treated cultures. Fludarabine had significantly more inhibitory effect on bcl-2-expression than cytarabine in KGI-resistant myeloid leukaemia cells. Ajoene significantly enhanced the inhibitory effect of the two chemotherapeutic drugs, cytarabine and fludarabine, on bcl-2-expression in KGI cells. Bcl-2-expression could not be detected in fludarabine + ajoene-treated cultures. The Western blot of bcl-2-expression in KGI control and treated cells confirmed the quantitative ELISA measurements. Quantitative measurement of activated caspase-3 (pg per million cells) showed the two drugs, cytarabine and fludarabine, significantly increased the activated caspase-3 level in KGI myeloid leukaemia cells.
The addition of ajoene enhanced the activation of caspase-3 in both cytarabine- and fludarabine-treated KGI cells. In conclusion, the present results suggest a potential role for the combination of ajoene with fludarabine-based chemotherapy in the treatment of refractory and/or relapsed AML patients. Further studies are warranted to evaluate a similar enhancing effect for ajoene in blast cells from AML patients in primary cultures.
Epidemiological and laboratory studies provide insight into the anticarcinogenic potential of garlic and its constituent compounds. Both water- and lipid-soluble allyl sulfur compounds are effective in blocking a myriad of chemically induced tumors. Part of the protection from these compounds probably relates to a block in nitrosamine formation and metabolism. However, blockage in the initiation and promotion phases of the carcinogenicity of various compounds, including polycyclic hydrocarbons, provide evidence that garlic and its constituents can alter several phase I and II enzymes. Their ability to block experimentally induced tumors in a variety of sites including skin, mammary and colon, suggests a general mechanism of action. Changes in DNA repair and in immunocompetence may also account for some of this protection. Some, but not all, allyl sulfur compounds can also effectively retard tumor proliferation and induce apoptosis. Changes in cellular thiol and phosphorylation stains may account for some of these antitumorigenic properties. The anticarcinogenic potential of garlic can be influenced by several dietary components including specific fatty acids, selenium, and vitamin A. Since garlic and its constituents can suppress carcinogen formation, carcinogen bioactivation, and tumor proliferation it is imperative that biomarkers be established to identify which individuals might benefit most and what intakes can occur with ill consequences..
Epidemiological and laboratory studies provide insight into the anticarcinogenic potential of garlic and its constituent compounds. Both water- and lipid-soluble allyl sulfur compounds are effective in blocking a myriad of chemically induced tumors. Part of the protection from these compounds probably relates to a block in nitrosamine formation and metabolism. However, blockage in the initiation and promotion phases of the carcinogenicity of various compounds, including polycyclic hydrocarbons, provide evidence that garlic and its constituents can alter several phase I and II enzymes. Their ability to block experimentally induced tumors in a variety of sites including skin, mammary and colon, suggests a general mechanism of action. Changes in DNA repair and in immunocompetence may also account for some of this protection. Some, but not all, allyl sulfur compounds can also effectively retard tumor proliferation and induce apoptosis. Changes in cellular thiol and phosphorylation stains may account for some of these antitumorigenic properties. The anticarcinogenic potential of garlic can be influenced by several dietary components including specific fatty acids, selenium, and vitamin A. Since garlic and its constituents can suppress carcinogen formation, carcinogen bioactivation, and tumor proliferation it is imperative that biomarkers be established to identify which individuals might benefit most and what intakes can occur with ill consequences.
Alliinase (EC 4.4.1.4) catalyses the production of allicin (thio-2-propene-1-sulfinic acid S-allyl ester), a biologically active compound which is also responsible for the characteristic smell of garlic. It was demonstrated that alliinase which contains 5.5–6% of neutral sugars, gives clear PAS-staining, binds to Con A and can form a complex with garlic mannose-specific lectin (ASA). Evidence that the formation of such a complex is mediated by the interaction of the carbohydrate of the glycoprotein enzyme with the lectin was obtained from a radioligand assay which demonstrated the binding of alliinase to ASA and competitive inhibition of this binding by methyl -d-mannoside. ASA I was shown as the lectin mainly present in the complex with alliinase. The results of this study also demonstrate that alliinase is glycosylated at Asn146 in the sequence Asn146-Met147-Thr148.
A variety of compounds derived from garlic bulbs have been shown in animal systems to possess anticancer properties. However, little information is available regarding the effectiveness of garlic in the prevention or treatment of human cancers. In the current study, we have assessed the ability of S-allyl cysteine (SAC), a derivative of aged garlic extract, to affect the proliferation and differentiation of LA-N-5 human neuroblastoma cells in vitro. Time-and dose-dependent inhibition of cell grow was observed in cultures treated with SAC for at least 2 days, with a half-maximal response at approximately 600 micrograms/ml. SAC treatment was unable to induce differentiation in neuroblastoma cells as assessed by morphological, biochemical and molecular markers. In addition, SAC was unable to potentiate the effects of retinoic acid and 8-bromo-cyclic AMP, agents known to promote differentiation of LA-N-5 cells. Our results indicate that SAC can inhibit human neuroblastoma cell growth in vitro. However, the apparent inability of this compound to induce differentiation may limit its therapeutic potential.
Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.(ABSTRACT TRUNCATED AT 250 WORDS)
The sulfur-containing compound ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) which arises from alliin, a cysteine derivative stored in garlic bulbs, was produced synthetically by decomposition of allicin. Its cytotoxic effect was tested using human primary fibroblasts (FS4), a permanent, non-tumorgenic cell line derived from baby hamster kidney cells (BHK21) and a tumorgenic lymphoid cell line derived from a Burkitt lymphoma (BJA-B). The cytotoxic action was in the range 2-50 micrograms/ml depending on the cell density. ED50 values, estimated on the basis of fmol ajoene/cell, revealed slightly higher doses for the primary cell (FS4) than the permanent line (BHK), whereas the tumorgenic BJA-B cells were most sensitive.
The present paper reports the chemopreventive action of garlic on 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin young adult Swiss albino mice. Insertion of sterile cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA inside the canal of uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experimental cervical carcinogenesis model system, if garlic was administered orally at the dose level of 400 mg/kg body wt./day for 2 weeks before and 4 weeks following carcinogen thread insertion. The cervical carcinoma incidence, as compared with that of the positive control (73%), was 23%. This decline in the incidence of carcinoma was highly significant (P less than 0.01). Hyperplastic and dysplastic changes did not show any definite correlation with the garlic treatment.
Six organosulfur compounds found in garlic were examined for their ability to alter the growth of canine mammary tumor cells (CMT-13) in culture. Water-soluble organosulfur compounds (S-allyl-cysteine, S-ethyl-cysteine and S-propyl-cysteine) did not significantly alter the growth of CMT-13 cells when added to cultures at 1.0 mM or less. However, oil-soluble organosulfur compounds (diallyl sulfide, diallyl disulfide and diallyl trisulfide) markedly inhibited growth. Increasing addition of diallyl disulfide (DADS) resulted in a progressive decrease in CMT-13 cell growth. Addition of glutathione before DADS markedly decreased the severity of the growth inhibition. Treatment with DL-buthionine-SR-sulfoxamine, a specific inhibitor of glutathione synthesis, accentuated the growth inhibition caused by DADS. These studies show that some organosulfur compounds found in garlic are effective inhibitors of the growth of the neoplastic CMT-13 cell. The inhibitory effects of these compounds are modified by intracellular glutathione.
The effect of garlic on the serum lipid profile has been the subject of controversy. This study was therefore designed to examine the effects of allicin, an active constituent of garlic, on the lipid profile in a rabbit model.
Allicin was produced by reacting alliin, synthesized in our laboratory, with purified alliinase. Nineteen New Zealand White rabbits were fed a cholesterol-rich diet (0.25% cholesterol) for 18 weeks. Ten rabbits received freshly produced allicin (3 mg/kg orally) starting at 8 weeks, and nine received placebo. There was no significant difference between the lipid profiles of the two groups at baseline up to 8 weeks.
From day 28 of allicin supplementation a significant difference was found between the allicin and placebo groups in the graph regression lines describing the influence of allicin on serum cholesterol: Y = 41.39 + 8.69 multiplied by day (control) versus Y = -877.24 + 17.67 multiplied by day (allicin). The same trend was found for low-density lipoprotein concentrations: Y = 10.3 + 8.4 multiplied by (control) versus Y = -750.4 + 15.7 multiplied by day (allicin). The serum high-density lipoprotein levels also differed significantly between the groups: Y = 20.29 + 0.24 multiplied by day (control) versus Y = -109.9 + 1.65 multiplied by day (allicin).
Our results indicate that allicin has a beneficial effect on the serum lipid profile in hyperlipidemic rabbits, and should be further tested clinically.
Most studies on garlic during the past 15 years have been primarily in the fields of cardiovascular and cancer research. Cardiovascular studies have been mainly related to atherosclerosis, where effects were examined on serum cholesterol, LDL, HDL, and triglycerides. Although the studies were not consistent in relation to the dosage, standardization of garlic preparations, and period of treatment, most findings suggest that garlic decreases cholesterol and triglycerides levels in patients with increased levels of these lipids. Lowering of serum lipids by garlic ingestion may decrease the atherosclerosis process. The other major beneficial effect of garlic is due to its antithrombotic actions. This field of garlic research has been extensively studied. Garlic extracts and several garlic constituents demonstrate significant antithrombotic actions both in vitro and in vivo systems. Allicin and adenosine are the most potent antiplatelet constituents of garlic because of their in vitro effects. Since both allicin and adenosine are rapidly metabolized in human blood and other tissues, it is doubtful that these compounds contribute to any antithrombotic actions in the body. In addition, ajoene also seems not to be an active antiplatelet principle, because it is not naturally present in garlic, garlic powders, or other commercial garlic preparations. Only a small amount of ajoene can be found in garlic oil-macerates; however, ajoene is being developed as a drug for treatment of thromboembolic disorders. Recent findings on the identification of potent enzyme inhibiting activities of adenosine deaminase and cyclic AMP phosphodiesterase in garlic extracts are interesting, and may have a significant role in the pharmacological actions in the body. Presence of such enzyme inhibitors in garlic may perhaps explain several clinical effects in the body, including the antithrombotic, vasodilatory, and anticancer actions. Epidemiological studies have suggested that garlic plays a significant role in the reduction of deaths caused by malignant diseases. This had led many investigators to examine garlic and garlic constituents for their antitumor and cytotoxic actions both in vitro and in laboratory animals. The data from these investigations suggest that garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. In summary, the epidemiological, clinical, and laboratory data have proved that garlic contains many biologically and pharmacologically important compounds, which are beneficial to human health from cardiovascular, neoplastic, and several other diseases. Numerous studies are in progress all over the world to develop effective and odorless garlic preparations, as well as to isolate the active principles that may be therapeutically useful.
Overall, several investigations indicate that garlic and its organic allyl sulfur components inhibit the cancer process. Furthermore, these studies reveal that the benefits of garlic are not limited to a specific species, a particular tissue, or a specific carcinogen. Finally, odor is not a prerequisite for the protection provided by garlic against the initiation of chemical carcinogenesis. Although the water-soluble compound S-allyl cysteine is effective in reducing the risk of chemically induced tumors in experimental animals, it has no effect on established tumors. However, oil-soluble compounds such as diallyl disulfide are effective in reducing the proliferation of neoplasms. Although the evidence supports the benefits of garlic, additional evidence is needed to determine the quantity needed by humans to minimize cancer risk.
Organosulfur compounds are the biologically active components of allium vegetables. Many health benefits have been ascribed to them, including inhibition of carcinogenesis. Inasmuch as several of these thioallyl compounds are quite unstable and others are rapidly inactivated in the body, we have investigated one of the stable components present in aged garlic extract, S-allylmercaptocysteine (SAMC), in an effort to determine whether it can inhibit proliferation of cancer cells. Proliferation and viability of two erythroleukemia cell lines, HEL and OCIM-1, two hormone-responsive breast and prostate cancer cell lines, MCF-7 and CRL-1740, respectively, and normal human umbilical vein endothelial cells in response to different concentrations of SAMC were studied for up to two weeks. There were variations in sensitivity to this organosulfur compound in the different cell lines examined, but the two hormone-responsive cancer cell lines of breast and prostate clearly were far more susceptible to the growth-inhibitory influence of the thioallyl compound. The antiproliferative effect of SAMC was limited to actively growing cells. Human umbilical vein endothelial cells that had reached confluence escaped the reduction in viability so noticeable in the cancer cell lines tested. Our studies thus give evidence of a direct effect of SAMC on established cancer cells.
The pharmacological role of garlic in prevention and treatment of cancer has received increasing attention, but thorough investigations into the molecular mechanisms of action of garlic compounds are rare. The present study demonstrates that ajoene, a major compound of garlic induces apoptosis in human leukemic cells, but not in peripheral mononuclear blood cells of healthy donors. The effect was dose and time dependent. Apoptosis was judged by three criteria, morphology of cells, quantification of subdiploid DNA content by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. Ajoene increased the production of intracellular peroxide in a dose- and time-dependent fashion, which could be partially blocked by preincubation of the human leukemic cells with the antioxidant N-acetylcysteine. Interestingly, N-acetylcysteine-treated cells showed a 50% loss of ajoene-induced apoptosis. Moreover, ajoene was demonstrated to activate nuclear translocation of the transcription factor nuclear factor kappaB, an effect that was abrogated in N-acetylcysteine-loaded cells. These results suggested that ajoene might induce apoptosis in human leukemic cells via stimulation of peroxide production and activation of nuclear factor kappaB. This is a novel aspect in the biological profile of this garlic compound and an important step in elucidating the underlying molecular mechanisms of its antitumor action.
A number of naturally occurring products from vegetables and herbs exert chemopreventive properties against carcinogenesis. In this paper, two such compounds, isolated from garlic and from a traditional Chinese medicinal herb, are described for review. Elemene, isolated from the Chinese medicinal herb Rhizoma zedoariae, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo. This novel antineoplastic agent has substantial clinical activity against various tumors. The in vitro effect of elemene on the growth of leukemia cells was evaluated by MTT assay. The IC50 values of elemene for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were 27.5 micrograms/mL and 81 micrograms/mL, respectively, while IC50 for peripheral blood leukocytes (PBL) was 254.3 micrograms/mL. The inhibitory effect of elemene on proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M phase transition and with induction of apoptosis. The apoptosis of tumor cells was confirmed by DNA ladder formation on gel electrophoresis and characteristic ultrastructural alterations. The results also demonstrated that inhibitory effects of allicin, a natural organosulfide from garlic, on proliferation of tumor cells were associated with the cell cycle blockage of S/G2M boundary phase and induction of apoptosis. These findings suggest that induction of apoptosis may contribute to the mechanisms of antitumor activity of elemene and allicin, which merit investigation as potential chemoprevention agents in humans.
Epidemiological studies in China provide reason to suspect that a rich garlic content in the diet might reduce the proliferation of tumors in humans. We conducted experiments on human tumor cell lines and determined the influence of a garlic powder preparation, a garlic extract (reported as 8-10% L(+)-alliin enriched), and a combination thereof, on cellular proliferation in cell cultures, employing the widely used indirect neutral red procedure. Garlic powder failed to inhibit the growth of human hepatoma HepG2 or human colorectal carcinoma Caco2 cells at concentrations of up to 1000 micrograms/ml. Garlic extract, in which the alliin content was highly enriched was also unable to inhibit the growth of these cells. However, when the garlic extract was supplemented with garlic powder (to 10% final concentration) there was a concentration-dependent clear inhibition of tumor cell growth (IC50 values of 330 micrograms/ml for HepG2 and 480 micrograms/ml for Caco-2 cells). The growth of the human lymphatic leukemia cell line CCRF CEM was significantly inhibited in a dose-dependent manner by both garlic powder and garlic extract at concentrations as low as 30 micrograms/ml. However, no potentiation of this effect occurred upon mixing of the two preparations. Our results suggest that the antiproliferative effects of garlic may be due to breakdown products of alliin, such as allicin or polysulfides, rather than alliin itself, since the addition of an alliinase system (garlic powder) to an alliin enriched preparation without alliinase (garlic extract) potentiated the effects observed with the two preparations alone.
The metabolism of diallyl disulfide (DADS), a garlic sulfur compound, was investigated in human liver microsomes. Diallyl thiosulfinate (allicin) was the only metabolite observed and its formation followed Michaelis-Menten kinetics with a Km = 0.61 +/- 0.2 mM and a Vmax = 18.5 +/- 4.2 nmol/min/mg protein, respectively (mean +/- S.E. M., n = 4). Both flavin-containing monooxygenase and the cytochrome P-450 monooxygenases (CYP) were involved in DADS oxidation, but the contribution of CYP was predominant. The cytochrome P-450 isoforms involved in this metabolism were investigated using selective chemical inhibitors, microsomes from cells expressing recombinant CYP isoenzymes, and studying the correlation of the rate of DADS oxidation with specific monooxygenase activities of human liver microsomes. Diethyldithiocarbamate and tranylcypromine inhibited allicin formation, whereas other specific inhibitors had low or no effect. Most of the different human microsomes from cells expressing CYP were able to catalyze this reaction, but CYP2E1 showed the highest affinity with a substantial activity. Furthermore, allicin formation by human liver microsomes was correlated with p-nitrophenol hydroxylase activity, a marker of CYP2E1, and tolbutamide hydroxylase activity, a marker of CYP2C9. Among these approaches only CYP2E1 was identified in each case, which suggested that DADS is preferentially metabolized to allicin by CYP2E1 in human liver. However the minor participation of other CYP forms and flavin-containing monooxygenases is likely.
Garlic (Allium sativum) and onion (Allium cepa) are among the oldest of all cultivated plants. Additionally, both plants have been used as medicinal agents for thousands of years. Both garlic and onion have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focussed on the beneficial and medicinal properties of garlic and onions. In particular, the use of these agents in the treatment and prevention of cardiovascular disease and cancer is an area of considerable investigation and interest.
We describe an enzyme-linked immunosorbent assay (ELISA) for quantifying relative amounts of active caspase 3 in apoptotic cells. Covalent modification of caspase 3 active sites with a biotinylated inhibitor differentiates active from latent caspases. Capture on an ELISA plate with an antibody specific for caspase 3 makes the assay specific for caspase 3. Detection is with horseradish peroxidase (HRP)-conjugated streptavidin that binds to the biotinylated inhibitor covalently bound to caspase 3. Using the assay we detected 6.6 ng active caspase 3 per 10(6) apoptotic staurosporine-treated Jurkat cells. Specificity of the assay for caspase 3 was demonstrated by lack of signal with purified caspases 2, 7, 8, and 10 that were modified by a biotinylated inhibitor. Specificity was also demonstrated by lack of signal with apoptotic MCF-7 cells which do not express caspase 3. The ability to discriminate between active and latent caspase 3 was shown by Western blotting with HRP-streptavidin and anti-caspase 3. Although latent caspase 3 was captured it was not covalently modified with the biotinylated inhibitor. The basic principle of using a covalent inhibitor to identify active enzymes and an antibody to differentiate between enzymes with similar activities has potential for quantifying active members of many classes of enzymes.
The objective of this review is to examine briefly the medical uses of garlic throughout the ages and the role that it was considered to play in prevention and treatment of disease. Interest in the potential benefits of garlic has origins in antiquity and is one of the earliest documented examples of plants employed for treatment of disease and maintenance of health. Garlic was in use at the beginning of recorded history and was found in Egyptian pyramids and ancient Greek temples. There are Biblical references to garlic. Ancient medical texts from Egypt, Greece, Rome, China and India each prescribed medical applications for garlic. In many cultures, garlic was administered to provide strength and increase work capacity for laborers. Hippocrates, the revered physician, prescribed garlic for a variety of conditions. Garlic was given to the original Olympic athletes in Greece, as perhaps one of the earliest "performance enhancing" agents. It is of interest that cultures that developed without contact with one another came to similar conclusions about the efficacy of garlic. Modern science is tending to confirm many of the beliefs of ancient cultures regarding garlic, defining mechanisms of action and exploring garlic's potential for disease prevention and treatment.
The diverse health benefit effects of garlic include its anticancer activity. However, very little is known about such activity of isolated garlic compounds, among which allicin (the major ingredient of crushed garlic) has been the least studied. The aim of this work was to determine whether pure allicin exhibits the antiproliferative effect reported for garlic in in vitro models. Allicin, but not its precursor alliin, inhibited proliferation of human mammary (MCF-7), endometrial (Ishikawa), and colon (HT-29) cancer cells (50% inhibitory concentration = 10-25 microM). Two of three tested primary lines of human fibroblasts displayed a similar response to allicin (50% inhibitory concentration = 16-40 microM), whereas the third line was almost unaffected by this compound. The pure allicin and water extract of garlic powder with equivalent allicin concentrations displayed a similar potency, suggesting that allicin is responsible for the antiproliferative effect of the extract. The growth inhibition was accompanied by accumulation of cells in the G0/G1 and G2/M phases of the cell cycle (MCF-7 cells) and not by a significant increase in cell death. Allicin caused a transient drop in the intracellular glutathione (GSH) level, the magnitude and kinetics of which significantly varied depending on cell type. The extent of the decrease in GSH levels correlated well (r = 0.75) with the growth inhibitory activity of allicin. On the basis of these findings, we suggest that allicin plays a major role in the antiproliferative effect of water-soluble garlic preparations and that this effect may be attributed to the ability of allicin to transiently deplete the intracellular GSH level.
Diallyl disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventative activity against colon, lung, and skin cancers. However, its molecular mechanism of action is still obscure. The present study demonstrated that DADS induces apoptosis of human leukemia HL-60 cells in a concentration- and time-dependent manner with an IC50 for cell viability of less than 25 microM. DADS activated caspase-3 as evidenced by both the proteolytic cleavage of the proenzyme and increased protease activity. Activation of caspase-3 was maximal at 3 hr and led to the cleavage of 116 kDa poly(ADP-ribose) polymerase (PARP), resulting in the accumulation of an 85 kDa cleavage product. Both activation of caspase-3 and cleavage of PARP were blocked by pretreatment with either antioxidants or a caspase-3 inhibitor, but not a caspase-1 inhibitor. DADS increased the production of intracellular hydrogen peroxide, which was blocked by preincubation with catalase. These results indicate that DADS-induced apoptosis is triggered by the generation of hydrogen peroxide, activation of caspase-3, degradation of PARP, and fragmentation of DNA. The induction of apoptosis by DADS may be the pivotal mechanism by which its chemopreventative action against cancer is based.
Every cell in a multicellular organism has the potential to die by apoptosis, but tumour cells often have faulty apoptotic pathways. These defects not only increase tumour mass, but also render the tumour resistant to therapy. So, what are the molecular mechanisms of tumour resistance to apoptosis and how can we use this knowledge to resensitize tumour cells to cancer therapy?
The apoptosis-inducing capacity of aqueous garlic extract during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamsters using DNA fragmentation and the apoptosis-associated proteins, tissue transglutaminase (tTG) and Bcl-2. Hamsters were divided into four groups of six animals each. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three times a week for 14 weeks. Group 2 animals painted with DMBA as in group 1, in addition received 250 mg/kg body weight aqueous garlic extract orally on days alternate to DMBA application. Group 3 animals received garlic extract as in group 2. Group 4 animals received neither DMBA nor garlic extract and served as the control. The experiment was terminated at the end of 14 weeks. Administration of aqueous garlic extract (250 mg/kg body weight) to animals painted with DMBA inhibited DMBA-induced oral carcinogenesis as revealed by the absence of neoplasms, induction of tTG and inhibition of Bcl-2 expression. The results of the present study suggest that garlic may exert its chemopreventive effect by inducing apoptosis.
Garlic in Health, History and World Cuisine
- L Moyers
Moyers, L., 1996. Garlic in Health, History and World Cuisine. Suncoast
Press, St. Petersburg, FL.
Death and anti-death: tumour resistance to apoptosis
- Igney
Mechanisms and genes of cellular suicide
- Steller
Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention
- Zheng