Organo-Sulphur Garlic Compounds Influence Viability of Mammalian Cells: A Review (original) (raw)
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Biological properties of garlic and garlic-derived organosulfur compounds
Environmental and Molecular Mutagenesis, 2009
Medicinal properties of garlic (Allium sativum) have been widely known and used since ancient times till the present. Garlic enhances immune functions and has antibacterial, antifungal and antivirus activities. It is known to prevent platelet aggregation, and to have hypotensive and cholesterol-and triglyceride-lowering properties, although the latter features have been questioned. This review is focused on anticancer efficacy of Allium sativum, and attempts to explain the mechanisms of this action. Medicinal properties of garlic rely upon organosulfur compounds mostly derived from alliin. Organosulfur compounds originating from garlic inhibit carcinogen activation, boost phase 2 detoxifying processes, cause cell cycle arrest mostly in G2/M phase, stimulate the mitochondrial apoptotic pathway, increase acetylation of histones. Garlic-derived sulfur compounds influence also gap-junctional intercellular communication and participate in the development of multidrug resistance. This review presents also other little known aspects of molecular action of garlicderived compounds, like modulation of cellular redox state, involvement in signal transduction and post-translational modification of proteins by sulfane sulfur or by formation of mixed disulfides (S-thiolation reactions). Environ. Mol. Mutagen. 50:247-265, 2009. V V C 2009 Wiley-Liss, Inc.
Phytotherapy Research, 2011
Biological activity of garlic has been attributed to organosulfur compounds, most of all to oil-soluble allyl sulfides, such as diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS). This study evaluated the effectiveness of garlic-derived allyl sulfides in influencing peroxidative processes, levels of thiols and sulfane sulfur and its metabolic enzymes in normal mouse liver cells. Various allyl sulfides (DAS, DADS and DATS) dissolved in corn oil were given intraperitoneally to mice for 10 days. After sacrificing the mice, biochemical assays were performed in liver homogenates and in plasma in order to establish liver function. All allyl sulfides under study had a beneficial effect in the mouse liver since they decreased reactive oxygen species and malondialdehyde levels and increased glutathione S-transferase activity and non-protein sulfhydryl group level. Moreover, DADS and DATS elevated total sulfane sulfur pool and activity of sulfane sulfur biosynthetic enzymes. The increase in sulfane sulfur level entailed augmentation of its antioxidant and regulatory capacities. Garlic-derived allyl sulfides exhibited antioxidant action in the liver and elevated anaerobic cysteine metabolism leading to the formation of sulfane sulfur-containing compounds. Thus, DADS and DATS showed beneficial action in the liver, which can be used for protection of normal liver cells during chemotherapy or for alleviation of liver damage. Copyright
Cell Biochemistry and Function, 2012
The aim of the present studies was to determine whether the mechanism of biological action of garlic-derived sulfur compounds in human hepatoma (HepG2) cells can be dependent on the presence of labile sulfane sulfur in their molecules. We investigated the effect of allyl sulfides from garlic: monosulfide, disulfide and trisulfide on cell proliferation and viability, caspase 3 activity and hydrogen peroxide (H 2 O 2 ) production in HepG2 cells. In parallel, we also examined the influence of the previously mentioned compounds on the levels of thiols, glutathione, cysteine and cysteinyl-glycine, and on the level of sulfane sulfur and the activity of its metabolic enzymes: rhodanese, 3-mercaptopyruvate sulfurtransferase and cystathionase. Among the compounds under study, diallyl trisulfide (DATS), a sulfane sulfur-containing compound, showed the highest biological activity in HepG2 cells. This compound increased the H 2 O 2 formation, lowered the thiol level and produced the strongest inhibition of cell proliferation and the greatest induction of caspase 3 activity in HepG2 cells. DATS did not affect the activity of sulfurtransferases and lowered sulfane sulfur level in HepG2 cells. It appears that sulfane sulfur containing DATS can be bioreduced in cancer cells to hydroperthiol that leads to H 2 O 2 generation, thereby influencing transmission of signals regulating cell proliferation and apoptosis. hydroperthiols with H 2 O 2 generation (Scheme 3). Sulfane sulfur from thiosulfoxide, which is a DADS isomer, does not show such properties. It indicates that only sulfane sulfur released from DATS in the form of hydroperthiol can produce biological activity in HepG2 cells restoring redox regulation, and this is not accompanied by formation of hydropersulfides of proteins.
Organosulfur compounds and possible mechanism of garlic in cancer
Saudi Pharmaceutical Journal, 2010
Garlic (Allium sativum), a member of the family Liliaceae, contains an abundance of chemical compounds that have been shown to possess beneficial effects to protect against several diseases, including cancer. Evidence supports the protective effects of garlic in stomach, colorectal, breast cancer in humans. The protective effects appear to be related to the presence of organosulfur compounds, predominantly allyl derivatives, which also have been shown to inhibit carcinogenesis in forestomach, esophagus, colon, mammary gland and lung of experimental animals. The exact mechanisms of the cancer-preventive effects are not clear, although several hypotheses have been proposed. Organosulfur compounds modulate the activity of several metabolizing enzymes that activate (cytochrome P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the formation of DNA adducts in several target tissues. Antiproliferative activity has been described in several tumor cell lines, which is possibly mediated by induction of apoptosis and alterations of the cell cycle. Organosulfur compounds in garlic are thus possible cancer-preventive agents. Clinical trials will be required to define the effective dose that has no toxicity in humans.
Anti-Cancer Agents in Medicinal Chemistry, 2014
Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of garlic reveal conflicting data as to pro-or anti-inflammatory responses depending on the particular experimental setups and the garlic preparation used (i.e. garlic extract versus chemically pure garlic compounds). Here we provide an overview of the chemistry of the major garlic organosulfur compounds, summarize the current understanding and propose a link between the immunomodulating activity of garlic and the prevention of cancer. We hypothesize that garlic rather elicits anti-inflammatory and anti-oxidative responses that aid in priming the organism towards eradication of an emerging tumor.
Journal of Nutrition & Intermediary Metabolism, 2018
Trichloromethane (TCM) serves as an ingredient in pesticide formulations and fire extinguishers. It is a reported hepato-and renal-toxin. We therefore investigated the chemo-preventive effect of diallyl disulfide (DADS) on TCM-induced hepatotoxicity. Twenty five rats, divided into five groups of five animals each were used. TCM at the dose of 200 mg/kg was orally administered, and concomitantly treated with DADS (50 mg/kg), 5 days per week for 3 weeks. Compared with control, there was a significant increase in hepatic expressions of nuclear factor kappa B (NFkB), TUNEL positive cells (apoptosis), and concentrations of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2), and nitric oxide (NO). Also, a significant decrease in expressions of p53, and activities of catalase (CAT) and glutathione peroxidase (GPx), as well as level of reduced glutathione (GSH) was recorded following TCM administration. Following treatment, DADS intervention significantly reduced the hepatic NFkB expressions, apoptotic positive cells as well as levels of MDA, H 2 O 2 , and NO, and also significantly increased the level of GSH, activities of CAT and GPx compared with TCM group, while its effect on expressions of p53 was insignificant. Hepato-protection by DADS against TCM-induced hepatotoxicity may therefore be via suppressions of NFkB activation, apoptosis, and oxidative stress in rats.
The Journal of nutrition, 2008
Much evidence in the last few years suggests that the antiproliferative effects of various garlic secondary metabolites in in vitro experimental systems are due to redox-based mechanisms. In particular, sulfur-containing allyl compounds have been demonstrated to generate reactive oxygen species and to modify directly the redox state of specific reactive cysteines on protein surfaces. On the basis of such properties, allyl compounds, in particular the ones present in the oil-soluble fraction of garlic extracts, can function as modulators of several redox-mediated signaling pathways related to the activation of mitogen-activated protein kinases, cell cycle, DNA repair, and cell demise. However, even though many in vitro studies have tried to dissect the mechanisms of action of garlic derivatives, research in this field is still incomplete and questions about bioavailability, biotransformation, and pro-oxidant activity are still unanswered. This review discusses recent findings on such...
Anti-Cancer Agents in Medicinal Chemistry, 2011
Organic sulfur compounds (OSCs) derived from plants, fungi or bacteria can serve as chemopreventive and/or chemotherapeutic agents and have been attracting medical and research interest as a promising source for novel anti-cancer agents. Garlic, which has long been used as a medicinal plant in different cultures due to its multiple beneficial effects, contains a consistent number of OSCs, the majority of which are currently under investigation for their biological activities. Experimental animal and laboratory studies have shown strong evidence that garlic OSCs may affect cancer cells by promoting early mitotic arrest followed by apoptotic cell death without affecting healthy cells. The ability of OSCs to hinder cancer cell proliferation and viability tightly correlates with the length of the sulfur chain. Current data support a mechanism of mitotic arrest of cancer cells due to the alteration of the microtubule network, possibly as a consequence of the high reactivity of sulfur atoms against the thiol groups of different cellular macromolecules controlling crucial regulatory functions. Taken together, these findings indicate a promising potential for the use of garlic-derived sulfur compounds in chemoprevention and chemotherapy.
Journal of Applied Pharmaceutical Science, 2018
Background: Garlic (Allium sativum) with its main component organosulfur compounds (OSCs) has an anticancer effect against a large verity of cancer cells. This anticancer effect was studied on individual garlic components, rather than fractions. Methods: Herein, we investigated the anticancer effect of different garlic fractions on the MCF7 and HepG2 cells and studied the underlying mechanism. Results: Different garlic fractions, extracted by methylene chloride (MC), petroleum ether (PE), ethyl acetate (EtOAc) and butanol (B) solvents, each alone exhibited significant dose-dependent anti-proliferative activity on MCF7 and HepG2 cells with best results for EtOAc with IC 50 values 21.32 and 26.22 µg/ml, respectively, as compared to vehicle-treated cells. HPLC analysis revealed the presence of 14 components in EtOAc fraction with highest concentrations for linoleic acid (LA) and S-allylthiocysteine (SAC). EtOAc fraction inhibited cancer cells proliferation through induction of apoptosis (revealed by a significant increase in mRNA levels of apoptotic markers, Caspase 3 and Bax and a significant decrease in mRNA levels of the anti-apoptotic marker, Bcl2) and cell cycle arrest in G2/M phase (indicated by increase in number of MCF7 and HepG2 cells in this phase). Conclusions: These in vitro results suggest that garlic EtOAc fraction or its main component could be used as an adjuvant to anticancer drug or can help in the development of new anticancer drugs based on components of this fraction.
Journal of Neurochemistry, 2007
In this study, we further examined the effects of diallyl disulfide (DADS), one of the major components of oil-soluble garlic extracts (GE) and of raw water GE on SH-SY5Y and NSC34 neuronal cell lines. Both treatments with DADS and GE were able to induce growth arrest and apoptosis, and we observed an increased flux of reactive oxygen and nitrogen species as early signs of cytotoxicity. We demonstrated that the content of neuronal nitric oxide synthase (nNOS) increased as early as 1 h of treatment demonstrating to be a very early sensor of DADS and GE cytotoxicity. Treatments with L-nitropropyl-arginine, an inhibitor of nNOS, increased the rate of apoptosis whereas the overexpression of nNOS significantly reduced cell death by inhibiting DNA damage, protein oxidation, and the activation of the JNK/c-Jun apoptotic signaling cascade. Overall these results demonstrate that garlic derivatives may modulate nNOS and suggest an important contribution of nitric oxide in counteracting their reactive oxygen species-mediated cytotoxicity.