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Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells

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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.

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... -Others antitumor effects (chelating irons, ↓p38 adhesion of tumor cells and metastasis, growth inhibition, cell cycle arrest, ↑ROS production and damaging to lipids and proteins, ↓MMP, antiangiogenesis, block cellular aging, hindering cellular division by expression of p38, ↓autophagy, ↓side effects of chemotherapy and radiotherapy, AMPK/ TSC2 expression and beclin-1 signaling pathways) (Thomson & Ali, 2003), (Saedi, Md Noor, Ismail, & Othman, 2014), (Oommen, Anto, Srinivas, & Karunagaran, 2004) (Grudzien & Rapak, 2018), (Ishikawa et al., 2006), (Lestari & Rifa'i, 2018) (Saud et al., 2016;Ziaei et al., 2015), (Hodge, Hodge, & Han, 2002), (Guan, Zhao, Xie, & Zeng, 2018) (Belloir, Singh, Daurat, Siess, & Le Bon, 2006), (Knowles & Milner, 2003) (De Martino, Filomeni, Aquilano, Ciriolo, & Rotilio, 2006), (DeLeon, Gao, Huang, & Olson, 2016;Ueda et al., 2002), (Y.-L. Chu et al., 2013) (Belloir et al., 2006), (Yamazaki et al., 1992) (Saud et al., 2016;Ziaei et al., 2015), (Hodge et al., 2002) , (H.-S. ...
... In addition, ajoene is a good fighter against chronic myelogenous leukemia cells (Saedi et al., 2014). More researches around the anticancer activity of ajoene showed that this agent by inducing Bcl-2 inhibition and caspase 3 cleavage can improve the anticancer activity of cytarabine and fludarabine antileukemic drugs against CD34 + leukemic cancer cells (Oommen et al., 2004). ...
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Natural resources such as plants are an upright curing option in treating cancers and reducing the side effects of current therapeutic modalities. Allium genus vegetables are of the most interesting herbs in restricting cancers that includes garlic, onions, leeks, chives, and shallots. These plants have been exploited in folk medicine because of their beneficial health effects in improving numerous diseases. The phytochemical analysis of various Allium genus members showed that, to date, 16 species have proved potential anticancer properties due to the accumulation of various sulfur and organic compounds like S‐allyl mercaptocysteine, quercetin, flavonoids, and ajoene. These compounds with various mechanisms such as hindering cell cycle, inhibiting signaling pathways, inducing apoptosis, and antioxidant activity interfere with diverse stages of formation, growth, differentiation, and metastasis of cancer cells. Similar to garlic and onion, other species have exhibited anticancer activities, so that active natural molecules extracted from them might serve as possible anticancer agents. Therefore, evaluating the main ingredients and studying their anticancer mechanisms are of great importance. In this review, we aim to summarize the available data on anticancer mechanisms of 16 species of Allium genus and their major compounds to assist further researches on the treatment and prevention of cancers.
... 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). ...
Article
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.
... Research has revealed that allicin targets multiple pathways implied in the inhibition of cancer development [27], including cell cycle arrest [21,28], the induction of apoptosis [29][30][31][32][33][34], the induction of histone acetylation [35] and the inhibition of angiogenesis [36]. Some of these studies dealing with the induction of apoptosis by allicin have also been reported for Caco-2 and HT-29 [20,34,37]. ...
... Research has revealed that allicin targets multiple pathways implied in the inhibition of cancer development [27], including cell cycle arrest [21,28], the induction of apoptosis [29][30][31][32][33][34], the induction of histone acetylation [35] and the inhibition of angiogenesis [36]. Some of these studies dealing with the induction of apoptosis by allicin have also been reported for Caco-2 and HT-29 [20,34,37]. In our study, we also confirmed the induction of apoptosis in HT-29 cells incubated with the thiosulfinate-enriched Allium sativum extract for 24 h (see Table 2). ...
Article
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In this work, we sought to investigate the effects of a thiosulfinate-enriched garlic extract, co-administered with 5-fluorouracil (5-FU) or oxaliplatin chemotherapy, on the viability of colon cancer cells (Caco-2 and HT-29). We also addressed the economic feasibility of a new combined treatment of this thiosulfinate-enriched garlic extract, with oxaliplatin that could reduce the dosage and costs of a monotherapy. The thiosulfinate-enriched garlic extract not only enhanced the impact of 5-FU and oxaliplatin (500 µM) in decreasing Caco-2 and HT-29 viability, but also showed a higher effect than standard 5-FU and oxaliplatin chemotherapy as anti-cancer agents. These results provided evidences for the combination of lyophilized garlic extract and 5-FU or oxaliplatin as a novel chemotherapy regimen in colon cancer cells that may also reduce the clinical therapy costs.
... Antimalarial treatment is dependent on chemical synthetic drugs which are facing development of resistance. Allium sativum or garlic has long been known and applied in daily life for various purposes as it contains various medical properties and elements that can be utilised to treat various diseases among many communities in the world (Gurusubrammaniam et al., 1997, Oommem et al., 2004. Somehow, very limited information was available regarding its properties towards antimalarial activities. ...
... Somehow, very limited information was available regarding its properties towards antimalarial activities. On top of exhibiting antibacterial, antifungal and anticancer properties (Moazeni & Nazer, 2010, Oommem et al., 2004, scientifically documented, garlic extracts are also outstanding inhibitor towards the growth of some important blood flagellated protozoa such as Trypanosoma brucei and Leishmania donovani (Ramos et al., 2006), as well as Entamoeba histolytica and Trichomonas vaginalis (Saleehen et al., 2004). ...
Article
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Garlic or Allium sativum is widely applied as alternative medicine and in ethnopharmacological studies. This study was done to evaluate the antimalarial properties of aqueous extract of garlic against Plasmodium berghei NK65. The groups of male ICR mice were intraperitoneally (i.p) infected with 0.1 mL of 1 × 10 7 parasitised red blood cells (RBC) before being orally given pre-and post-infection treatments with 0.2 mL of 100 mg/kg body weight (bw) of freeze-dried aqueous garlic extract. Parasitemia was microscopically examined and measured by Giemsa stained thin blood smear. There was a positive correlation (p<0.05, n = 6) for all assessed parameters; parasitemia density (%), survival time (day) and the ability to inhibit the parasite growth (%) between pre-treated infected mice with the other groups. However, the value recorded was still lower compared to the mice treated with commercial antimalarial drug primaquine and chloroquine. However, biochemical parameters of treated animals were in the normal range indicative of no toxicity. Histological examination showed no abnormalities and injuries on the selected vital organs. This study proved garlic has potential as alternative antimalarial drug.
... 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. ...
Article
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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.
... 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). ...
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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
... 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. ...
Article
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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.
... 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). ...
Article
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 . ...
Article
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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.
... 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). ...
Article
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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.
... The garlic compound found to induce apoptosis in tumor cells is allicin. It is reported that in cervical cancer cell lines, 1 or 10 µM allicin induces apoptosis via the caspase-dependent pathway [22]. In another study, a combination of 10 µM allicin with 0.1 or 1 µM paclitaxel-induced apoptosis in MCF-7 breast cancer cells [23]. ...
Article
Breast cancer is the most frequent cancer in women worldwide and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo‐sulfur compounds, especially alliin and allicin. Here, we evaluated in luminal A and triple‐negative breast cancer cells, the effects of both molecules on cell death and senescence, we also assessed their senolytic potential. MCF‐7 (luminal A) and HCC‐70 (triple‐negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC‐10 fluorometric assay kit. Apoptosis‐related genes were evaluated by RT‐PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (β‐Galactosidase Staining) and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspases ‐3, ‐8 and ‐9 activation, upregulation of NOXA, P21 and BAK, as well as downregulation of BCL‐XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence and did not exhibit pro‐apoptotic effects in breast cancer cells.
... Previous research from Oommen et al. and Li et al. explained that Allicin's ability to increase EPC proliferation turned out to be in line with increasing dose, concentration, and time. EPC proliferation will be optimal by giving Allicin a dose of 40-50 Pg/ml but at doses above 50 Pg/ml it will cause condensation from the cell nucleus and form apoptotic bodies which are characteristic of apoptosis [8,13]. In this study, we had similar results in which low, moderate, and high doses can increase EPC proliferation. ...
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The reduced number and function of Endothelial Progenitor Cells (EPC) in stable coronary artery disease (SCAD) patients aggravate endothelial dysfunction and inhibit neovascularization, thus leading to atherosclerosis. Garlic is currently believed to increase the number and function of EPCs. Therefore, this in vitro study was conducted to analyse the effect of garlic extract ( Allicin ) on the proliferation of EPCs in patients with SCAD. Mononuclear cells were isolated from peripheral blood of eight SCAD patients and cultured on CFU-Hill media for three days. Samples were divided into 2 groups: a group treated with Allicin and a control group. The treatment group was then divided into 3 subgroups which received 10, 50, and 100 mg/ml of doses and incubated for 48 hours. EPC proliferation was assessed using MTT Cell Proliferation Assay. Immunohistochemical method of CD34 ⁺ were performed for EPC identification. Data was analysed using an independent T test and ANOVA. MTT Assay showed significant increase in EPC proliferation in Allicin group compared to control group (0.2811±0.008 vs 0.194±0.151, p<0.05) and significant improvements were observed in each dose increment. CFU-Hill quantification shows the addition of EPC colony in high-dose Allicin . Immunohistochemical method shows positive CD34 ⁺ expression. Allicin increases EPC proliferation dose-dependently from peripheral blood of SCAD patients.
... Ajoene-induced blood cancer cells HL60 are arrested in G(2)/M phase in cell cycle analysis and finally produces apoptosis. Oommen et al. [31] have showed that allicin stopped the growth of cancer cells in animal and humam model. It is demonstrated that allicin helped to form apoptotic bodies and nuclear condensation process and a DNA ladder in tumor cells. ...
... The direct inhibition of the the expression of anti-apoptotic proteins is another mechanism to promote cancer cell apoptosis, as demonstrated by various studies on the effect of ajoene on apoptosis in leukemia cells [24,25]. Similarly, induction of apoptosis by reduced expression of pro-apoptotic proteins such as Bcl-2 and Bcl-XL, reduced Bcl-2/Bax interaction, elevated caspase-3, -8, and -9 activity, increased cytochrome C release, and increased Apaf- 1 [19,38,39,40,41], and SAMC [42]. ...
Article
Background: Garlic, or Allium savitum, has long been used to treat various diseases, including cancer. The anticancer effects of garlic are linked to the several garlic-derived organosulfur compounds, such as allicin, ajoene, DAS, DADS, DATS, and SAMC. Animal and in vitro studies have demonstrated that garlic bioactive compounds may prevent cancer through mechanisms such as inducing cell cycle arrest, promoting apoptosis, and inhibiting angiogenesis in different cancer cells. Observational studies, including case-control and cohort studies, have been conducted to confirm the protective effect against colorectal, gastric, and other cancers associated with garlic-derived bioactive compounds and raw garlic consumption, but results have been mixed. Analysis of cell and animal model studies and epidemiological studies using the FDA’s evidence-based review system for health claims and FFC’s proposed standard for evaluating and developing functional food, it has been concluded that garlic cannot yet be considered as a functional food primarily due to the inconclusive data from observational studies and insufficient evidence from randomized clinical trials. Keywords: Garlic, cancer, allicin, bioactive compound, functional food
... The cysteine sulfoxides change to thiosulfinates, such as allicin (Cavallito and Bailey, 1944;, by the reaction with enzyme called alliinase (Ellmore and Feldberg, 1994) when the tissues of Allium plants are broken. Allicin has been reported to have several biological effects (Gebhardt et al., 1994;Briggs et al., 2000;Cañizares et al., 2004;Oommen et al., 2004;Arditti et al., 2005). However, unstable thiosulfinates including allicin are changed to organosulfur compounds, such as ajoene (Block et al., 1984), methyl 1-(methylthio)ethyl disulfane, and 5,7-diethyl-1,2,3,4,6-pentathiepane (Kuo et al., 1990). ...
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Five new cyclic organosulfur compounds, foliogarlic disulfanes A1 (1), A2 (2), and A3 (3) and foliogarlic trisulfane A1 (4) and A2 (5), were isolated from the leaves of Allium sativum (garlic). The chemical structures of these compounds were elucidated on the basis of physicochemical evidence including Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). Compounds 1–5 were obtained as complex compounds with disulfane or trisulfane and tetrahydro-2H-difuro[3,2-b:2′,3′-c]furan-5(5aH)-one. In addition, the hypothetical biosynthetic pathways of these compounds were suggested.
... out by Jeong et al. 35 revealed the role of Doenjang prepared by various starter culture on the up and down regulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl2), respectively, in a murine model of colitis-associated colon carcinogenesis. In addition, several published reports have indicated the role of garlic in induction of apoptosis via various molecular mechanisms 33,36 . However, to the best of our knowledge, it is the first report representing the effect of garlic-supplemented Doenjang on alterations in mitochondrial membrane potential and ability on colony formation. ...
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Three different forms of garlic, namely, fresh garlic (2%, 6%, 10%), heat-dried (1%, 2%, 3%) and freeze-dried (1%, 2%, 3%), were supplemented in soybean paste to prepare Doenjang and further evaluated for functional, nutritional and safety aspects. Results showed a considerable antioxidant and anti-proliferative activity of garlic-supplemented Doenjang. As a measure of nutritive value, a high amount of total free amino acids, 4,290.73 mg/100 g–5,492.94 mg/100 g, was observed in prepared Doenjang. Among all preparations, 3% freeze-dried garlic-supplemented Doenjang proved the most effective against gastric adenocarcinoma and lung adenocarcinoma with 50% inhibition concentration of 7.66 ± 0.53 mg/mL and 7.82 ± 0.34 mg/mL, respectively. However 10% fresh-garlicsupplemented Doenjang (GGD-10) showed better activity against colorectal adenocarcinoma (HT29) cell line. Furthermore, GGD-10 effectively reduced colony formation and altered mitochondrial membrane potential of HT29 cells. Absence of pathogenic bacteria (Staphylococcus aureus, Salmonella species and Bacillus cereus) and aflatoxin was observed in Doenjang samples. In addition, nontoxic amount of anti-nutritional biogenic amines was observed in all the samples. The results collectively suggest that the addition of garlic in Doenjang can improve its nutritional and functional value, resulting in the protection of consumers from protein deficiencies and various stress conditions.
... In this study, we found low levels of some sulphides in the garlic extracts that could still be noteworthy (Figs. 2 and 3): 3-vinyl-1,2-dithiacyclohex-4-ene (0.98% in 'Hongqixing', 0.16% in 'Ershuizao'), 3-vinyl-1,2-dithiacyclohex-5-ene (1.14% in 'Taicangbaipi', 4.46% in 'Hongqixing', 1.48% in 'Ershuizao'), and DATS (0.74% in 'Taicangbaipi', 1.64% in 'Hongqixing', 0.38% in 'Single-clove'). Many studies have shown that garlic has an inhibitory effect on microorganisms (Curtis et al., 2004;Mirik & Aysan, 2005;Slusarenko, Patel & Portz, 2008), and the bacteriostatic effect of garlic is known to be related to its organic sulphur compounds (Cavallito, Buck & Suter, 1944;Oommen et al., 2004). The difference in the sizes of the inhibition zones in Fig. 4 may be associated with the presence of these sulphides. ...
Article
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Garlic is used as a medicinal seasoning worldwide. The aim of this work was to compare four varieties of garlic: ‘Taicangbaipi’, ‘Ershuizao’, ‘Hongqixing’, and ‘Single-clove’; among them, ‘Ershuizao’ and ‘Hongqixing’ are unique to the Sichuan Province of China. Firstly, soluble sugar, starch, and the protein content of the garlic were analysed. There was more soluble sugar in ‘Single-clove’, total starch in ‘Hongqixing’, and protein content in ‘Ershuizao’ relative to the other three varieties, respectively. Gas chromatography–mass spectrometry analysis showed that ‘Ershuizao’ and ‘Hongqixing’ contained high levels of 5-hydroxymethylfurfural, which has antitumor, antioxidant, and cytoprotective effects. Indeed, the extracts from these two types of garlic were more effective at inhibiting tumour growth than that from the others. Moreover, the sulphide content and antimicrobial effects of ‘Ershuizao’ and ‘Hongqixing’ garlic were also higher than those of the other two types of garlic. In addition, changes observed in the membrane permeability and protein leakage suggest that the antimicrobial activity of the ‘Ershuizao’ and ‘Hongqixing’ extracts may be due to the destruction of the structural integrity of the cell membranes, leading to cell death.
... The ingradients in each curry, coconut milk, chicken was typical formula and showed difference in % Apoptosis induction clearly. Garlic was composed of Allicin [2] and derivative was Ajoene [3] had affected in inhibition of various cancer cells include Leukemia. Therefore the mixture of enzymes in simulation of gastrointestinal digestion was involved in Apoptosis process in Leukemia cell line. ...
Article
The combination of fresh herbs and spices used in curry pastes for Thai cooking were one of the uniqueness. Some of curry pastes with or without coconut milk and their ready-to-cook dishes have been scientifically proved for health benefits. Food samples were extracted with water or digested with the simulation of gastrointestinal digestion. The solutions of treated solutions were tested for Apoptosis induction and Necrosis on Leukemia cell line in vitro. The results of water extraction from all four curry pastes with coconut milk showed differences in Apoptosis induction and Necrosis of Leukemia cell line. Most of the water extraction from Jasmine rice/Thai spaghetti with curry pastes, coconut milk and chicken were higher potent than that of their curry pastes alone. After simulation of gastrointestinal digestion, Apoptosis induction and Necrosis of Leukemia cell line were higher than the water extraction. The curry pastes without coconut milk namely Gaeng Liang soup was shown to have greatest in Apoptosis induction among the other four curry pastes without coconut milk. Besides, Gaeng Liang soup also had the lowest in %Necrosis among the other curries without coconut milk.
... Allicin readily permeates cell membranes and is dose-dependently toxic to mammalian cells. Allicin induces apoptosis and inhibits cell proliferation at sublethal doses [9][10][11][12][13][14]. Allicin was reported early on to inhibit tumour growth in rats [15] and the anticancer effects of allicin have been confirmed repeatedly [16][17][18][19]. Indeed, a strategy to generate allicin in situ within tumour tissue was shown to be effective against a human tumour cell line https://doi.org/10.1016/j.freeradbiomed.2018.11.022 ...
Article
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A single clove of edible garlic (Allium sativum L.) of about 10 g produces up to 5 mg of allicin (diallylthiosulfinate), a thiol-reactive sulfur-containing defence substance that gives injured garlic tissue its characteristic smell. Allicin induces apoptosis or necrosis in a dose-dependent manner but biocompatible doses influence cellular metabolism and signalling cascades. Oxidation of protein thiols and depletion of the glutathione pool are thought to be responsible for allicin's physiological effects. Here, we studied the effect of allicin on post-translational thiol-modification in human Jurkat T-cells using shotgun LC-MS/MS analyses. We identified 332 proteins that were modified by S-thioallylation in the Jurkat cell proteome which causes a mass shift of 72 Da on cysteines. Many S-thioallylated proteins are highly abundant proteins, including cytoskeletal proteins tubulin, actin, cofilin, filamin and plastin-2, the heat shock chaperones HSP90 and HSPA4, the glycolytic enzymes GAPDH, ALDOA, PKM as well the protein translation factor EEF2. Allicin disrupted the actin cytoskeleton in murine L929 fibroblasts. Allicin stimulated the immune response by causing Zn²⁺ release from proteins and increasing the Zn²⁺-dependent IL-1-triggered production of IL-2 in murine EL-4 T-cells. Furthermore, allicin caused inhibition of enolase activity, an enzyme considered a cancer therapy target. In conclusion, our study revealed the widespread extent of S-thioallylation in the human Jurkat cell proteome and showed effects of allicin exposure on essential cellular functions of selected targets, many of which are targets for cancer therapy.
... On the other hand, in the case of extrinsic apoptosis, Caspase 8 is activated by signaling through death receptors and it can further activate Casp3, which is the common player in both apoptotic pathways. Moreover, Caspase 8 can cleave Bid and this event will further activate the mechanism of the intrinsic pathway [52,53]. ...
Article
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5-fluorouracil (5-FU) is an anticancer drug used to inhibit the proliferation of many different tumor cells. Since severe events are associated with this compound, its combination with different anticancer drugs or adjuvants would allow the use of a significantly lower dose of 5-FU. In this study, we highlighted that the combination of allicin with 5-FU inhibited the cell migration and proliferation of colorectal and lung cancer cells. 5-FU inhibited cell growth with a similar inhibitory concentration for both normal and tumor cells (~200µM), while allicin showed different inhibitory concentrations. With an IC50 of 8.625 µM, lung cancer cells were the most sensitive to allicin. Compared to 5-FU and allicin single-agent treatments, the co-treatment showed a reduced viability rate, with p < 0.05. The morphological changes were visible on all three cell lines, indicating that the treatment inhibited the proliferation of both normal and tumor cells. We highlighted different cell death mechanisms-apoptosis for lung cancer and a non-apoptotic cell death for colorectal cancer. The synergistic antitumor effect of 5-FU combined with allicin was visible against lung and colorectal carcinoma cells. Better results were obtained when a lower concentration of 5-FU was combined with allicin than the single-agent treatment at IC50.
... Allicin is a major bioactive compound of freshly crushed garlic (Allium sativum). A number of studies have shown that allicin has antimicrobial [1], antiinflammatory [2], as well as anticancer activities [3][4][5] in a wide range of cancer cell types. ...
Article
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Glioblastoma is the most aggressive cancer that occurs in the brain and spinal cord. In the present study, we investigated the effect of allicin, an organosulfur compound obtained from garlic (Allium sativum), on glioblastoma cell growth. When human glioblastoma DBTRG-05MG cells were incubated with different concentrations of allicin for 24 h, cell growth was suppressed in a dose-dependent manner. The results from image-based cytometer assays suggested that allicin caused S and G2/M phase cell cycle arrest and induced apoptosis. Autophagy detection studies showed that allicin also promoted this mechanism. Because cell migration is a key process during tumor formation, the effect of allicin on glioblastoma cell migration was also examined. After allicin treatment, the migration ability of cells decreased when compared with the control after 24 h. Taken together, the present results suggested that allicin inhibited human glioblastoma cell growth by inducing S and G2/M phase cell cycle arrest, apoptosis and autophagy. Our findings suggest that allicin suppressed glioblastoma cell growth through multiple target pathways. Therefore, allicin potentially serves as an alternative therapeutic candidate or could be synergistically used in combination with the standard drug for the treatment of glioblastoma multiforme.
... Several studies have indicated that compounds in garlic have wide-ranging health benefits, especially hypolipidemic and hypoglycemic properties [31]. Allicin, one of the major components of garlic, is well known for its anticarcinogenic effect [32,33]. Although allicin enhances thermogenesis by increasing UCP content in BAT [34], the exact mechanism by which allicin induces the formation of brown-like adipocytes is still unclear. ...
Article
Under specific conditions, white adipose tissue (WAT) depots are readily converted to a brown-like state, which is associated with weight loss. However, whether diet-derived factors directly induce browning of white adipocytes has yet to be established. Thus, we investigated the effects of allicin, one of the major components of garlic, on brown-like adipocyte formation in inguinal WAT (iWAT), and prevention of obesity and related complications in animal models. Allicin significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1) in differentiated mouse embryonic fibroblast cell line 3T3-L1 and differentiated iWAT stromal vascular cells (SVC), suggesting that allicin induced brown-like adipocyte formation in vitro. Concomitantly, allicin markedly enhanced the protein expression of KLF-15 and its interaction with UCP-1 promoter region. Such changes were absent in cells lacking KLF-15, suggesting the critical role of KLF15 in allicin action. Allicin also induced brown-like adipogenesis in vivo along with the appearance of multilocular adipocytes, increased UCP1 expression and increased lipid oxidation. In summary, our data suggest that allicin potentially prevents obesity and associated metabolic disorders such as type 2 diabetes mellitus by enhancing the expression of brown adipocyte-specific genes, including UCP-1, through KLF15 signal cascade.
... Sulfuric compounds, like allicin, have a different effect on cell signaling pathways. Allicin inhibits cell growth and induces apoptosis via the ERK-dependent pathway [31] or can activate both intrinsic and extrinsic apoptotic pathways [25,33,70]. Moreover, allicin can inhibit tumor cell progression by suppressing the HIF pathway [66]. ...
Article
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Allium sativum L. (garlic bulbs) and Allium fistulosum L. (Welsh onion leaves) showed quantitative differences of identified compounds: allicin and alliin (380 µg/mL and 1410 µg/mL in garlic; 20 µg/mL and 145 µg/mL in Welsh onion), and the phenolic compounds (chlorogenic acid, p-coumaric acid, ferulic acid, gentisic acid, 4-hydroxybenzoic acid, kaempferol, isoquercitrin, quercitrin, quercetin, and rutin). The chemical composition determined the inhibitory activity of Allium extracts in a dose-dependent manner, on human normal cells (BJ-IC50 0.8841% garlic/0.2433% Welsh onion and HaCaT-IC50 1.086% garlic/0.6197% Welsh onion) and tumor cells (DLD-1-IC50 5.482%/2.124%; MDA-MB-231-IC50 6.375%/2.464%; MCF-7-IC50 6.131%/3.353%; and SK-MES-1-IC50 4.651%/5.819%). At high concentrations, the cytotoxic activity of each extract, on normal cells, was confirmed by: the 50% of the growth inhibition concentration (IC50) value, the cell death induced by necrosis, and biochemical determination of LDH, catalase, and Caspase-3. The four tumor cell lines treated with high concentrations (10%, 5%, 2.5%, and 1.25%) of garlic extract showed different sensibility, appreciated on the base of IC50 value for the most sensitive cell line (SK-MES-1), and the less sensitive (MDA-MB-231) cell line. The high concentrations of Welsh onion extract (5%, 2.5%, and 1.25%) induced pH changes in the culture medium and SK-MES-1 being the less sensitive cell line.
... 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]. ...
Article
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]. ...
Article
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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.
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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.
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Reactive oxygen and nitrogen species deposited by cold physical plasma are proposed as predominant effectors in the interaction between discharge and biomedical application. Most reactive species found in plasma sources are known in biology for inter- and intracellular communication (redox signaling) and mammalian cells are equipped to interpret the plasma derived redox signal. Such, considerable effort has been put on the investigation of potential clinical applications and the underlying mechanism, with a special emphasis on conditions orchestrated significantly via redox signaling. Among these, immune system control in wound healing and cancer control stands out with promising in vitro and in vivo effects. From the fundamental point of view, further insight in the interaction of the plasma-derived species with biological systems is desired to a) optimize treatment conditions, b) identify new fields of application, c) to improve plasma source design, and d) to identify the trajectories of reactive species. Knowledge on the biochemical reactivity of non-thermal plasmas is compiled and discussed. While there is considerable knowledge on proteins, lipids and carbohydrates have not received the attention deserved. Nucleic acids have been investigated profoundly, yet focusing on molecule functionality rather than chemistry. The data collected underline the efforts taken to understand the fundamentals of plasma medicine but also indicate “no man’s lands” waiting to be discovered.
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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.
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We synthesized a series of small symmetrical unsaturated disulfides by a multi-step reaction starting from organic alcohols, and we performed a preliminary test to evaluate the effect of these compounds on the viability of A549 lung cancer cells. The garlic-derived natural compound diallyl disulfide, known for its anticancer activity, was used as the lead compound in this study. We synthesized five DADS analogues having different carbon chain lengths and different positions of the double bonds. Two analogues exhibited a promising antitumor activity in vitro, and the allylic double bond did not seem to be the main driving force.
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p>Allicin is a sulfur compound found in genus Allium characterized by numerous biological and pharmacological properties. Melanocrommyum, the second largest subgenus of Allium , has about 10 sections and 82 species in Iran. In this study, allicin content of aerial part, aerial part fresh mass and allicin yield belonging to 17 wild populations of six species of Allium sect. Acanthoprason and Asteroprason growing in different region of Iran, were analyzed. Allicin content evaluation using HPLC method showed its variation between populations from 26.98 to 58.11 mg g<sup>-1</sup> FW, also showing that all the tested populations of Allium are rich in allicin. The average of aerial part fresh mass and allicin yield varied between populations from 0.49 g to 1.66 g and from 14 mg to 78 mg, respectively. The populations were classified in four major groups using dendrogram generated by UPGMA method of cluster analysis. However, grouping of populations was not completely related to species and geographical regions. This study is the first evaluation of allicin content in wild populations of Allium sect. Acanthoprason and Asteroprason in Iran. High amount of allicin in these populations make them a new sources of allicin.</p
Conference Paper
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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.
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We present an illustrative case of unintentional burns to the feet of a 15-month-old child following the application of raw garlic as a home remedy for fever. We provide an overview of the historical medicinal uses of garlic as well as its unintended adverse effects. This case underscores the importance of clinicians' ability to recognize unusual presentations of injury due to culturally based practices that require care in emergency settings. This is particularly important in patient populations for whom abusive etiology would be considered.
Article
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.
Background: Cancer is a multi‐factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat the cancer but such drugs show negative side effects on normal cells and causes severe toxicity. Methods: The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regards, garlic and its active compounds including diallyl sulphide, diallyl trisulfide, ajoene and allicin has been established to suppress the growth of cancer and killing of cancer cells. Result: The review concerns about garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, Garlic and its active compound was established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increased the expression of tumor suppressor genes, inhibition of angiogenesis process, induction of apoptosis and modulating various other genetic pathways. Conclusion: This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.
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Allicin, a chemical component of garlic, has strong antioxidant activity and is thought to exert antiaging effects in vitro. We investigated whether allicin treatment would protect porcine oocytes and embryos from postovulatory aging mediated by apoptosis and autophagy. The rates of oocyte survival and polar body extrusion in samples treated with 1 µM allicin (1 AL) were significantly higher than in untreated samples (0 AL). In addition, 1 AL prevented defects in spindle formation and chromosome alignment, as well as decreases in the expression of maturation markers, during in vitro aging. In this study, we considered allicin to be a regulator of autophagy rather than an antioxidant or antiapoptotic agent. At the embryo level, although the cleavage rate after parthenogenetic activation was similar in all groups, the blastocyst formation rate was higher in the 1 AL group than in the 0 AL group. Our findings demonstrate that allicin effectively prevents the deterioration of porcine oocytes during aging in vitro, and could therefore be used to improve the quality of aged oocytes used in in vitro experiments. Allicin effectively prevents the deterioration of porcine oocytes during aging in vitro. It is occur by regulating autophagy. These results indicates that allicin as an antiaging reagent is useful for assisted reproductive technology.
Chapter
Carbohydrates, the structural building blocks of genetic materials and vital source of energy, are integral part of the living cells as they play important roles in biological system, particularly in cellular and intracellular interactions. Since long back, a number of simple carbohydrates and their derivatives are used clinically for the successful treatment of various diseases. In addition to the structural diversity in carbohydrates (in terms of functional groups, linkages as well rings system), other important features such as hydrophilicity, low toxicity, biocompatibility, and bioavailability required to provide the optimum pharmacokinetics are truly inspiring. Thus, due to their prospective as drug molecules, pharmaceutical and diagnostic tool, they stimulate the medicinal chemists to explore them in order to get the diverse well-defined eccentric glycoconjugates for their complete chemical, biochemical, and pharmacological investigations. This chapter highlights the impact of diverse carbohydrates and their derivatives in drug discovery and development with their future perspectives.
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Background Liver cancer, a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed. Methods The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange –ethidium bromide staining, styox green assay and DNA interaction study. We also used tool for computational chemistry studies of isolated compounds with the tyrosine kinase. Results In MTT assay, the crude extract caused significant cytotoxic effect with IC50 of 34.14 ± 0.9 µg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 µg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 µg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5µg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity guided isolation led to the isolation of two compounds which were characterized as para–methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 µg/ml followed by 2 with IC50 18.52 ± 1.9 µg/ml. DMSO was used as negative control and doxorubicin as reference standard (IC50 1.3 ± 0.21 µg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange –ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity. Conclusion This study revealed that the plant extracts and isolated compounds posses promising anti-proliferative activity against HepG-2 cell lines via apoptotic cell death. Ds with the tyrosine kinase.
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Glioblastoma is the most common primary tumor of the central nervous system that develops chemotherapy resistance. Previous studies showed that Allicin could inhibit multiple cancer cells including glioblastoma, but the function of Allicin in glioblastoma is still unclear. Our work aimed to investigate the underlying molecular mechanism. The results showed that miR-486-3p levels were greatly increased in glioblastoma during Allicin treatment. Overexpression of miR-486-3p increased chemosensitivity to temozolomide (TMZ) in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-486-3p, and miR-486-3p overexpression prevented the protein translation of MGMT. Moreover, overexpression of MGMT restored miR-486-3p-induced chemosensitivity to TMZ. Taken together, our studies revealed that Allicin could upregulate miR-486-3p and enhance TMZ sensitivity in glioblastoma. The results suggested that in the future, Allicin can be used as an adjuvant therapy with TMZ to improve the prognosis of patients, and miR-486-3p may be a potential target for glioblastoma treatment to improve the curative effects.
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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.
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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.
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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..
Conference Paper
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.
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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.
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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.
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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)
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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.
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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.
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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.
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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.
Article
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.
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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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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?
Article
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