Garlic-Anticancer activity

Garlic-Anticancer activity

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Garlic Garlic Biological Activities

Garlic Biological Activities- Anticancer activity

Summary

Cancer Cancer is one of the main causes of deaths worldwide. Based on National Cancer Database and the Surveillance, Epidemiology, and End Results, about 16.9 million people were identified with cancer in 2019 and this number will probably rise to more than 22.1 million in 2030. The Food and Drug Administration’s evidence-based review system for the scientific evaluation of health showed no reliable evidence for the relation between garlic and a reduced risk of gastric, breast, and lung cancer. However, credible evidence for an association between garlic intake and colon, prostate, esophageal, larynx, oral, ovary, and renal cell cancers has been reported, even if all studies were observational and the number of such trials that are scientifically considered valid in this analysis is remarkably few and the number of subjects involved generally small. As a result, relations between garlic and reduction of risk of cancers are still uncertain.

 

Effects on carcinogen metabolism

Inhibition of metabolic activation of carcinogens: Some chemical carcinogens do not become active carcinogens until they have been metabolized by Phase I biotransformation enzymes, such as those belonging to the cytochrome P450 (CYP) family. Inhibition of specific CYP enzymes involved in carcinogen activation inhibits the development of cancer in some animal models. In particular, DAS and its metabolites have been found to inhibit CYP2E1 activity in vitro. and when administered orally at high doses to animals. Oral administration of garlic oil and DAS to humans has also resulted in evidence of decreased CYP2E1 activity.

Induction of Phase II detoxifying enzymes: Reactions catalyzed by phase II detoxifying enzymes generally promote the elimination of drugs, toxins, and carcinogens from the body. Consequently, increasing the activity of phase II enzymes, such as glutathione S-transferases (GSTs) and NQO-1, may help prevent cancer by enhancing the elimination of potential carcinogens (see the Nrf2-dependent antioxidant pathway).In animal studies, oral administration of garlic preparations and organosulfur compounds was found to increase the expression and activity of phase II enzymes in a variety of tissues. For example, DADS protected rodent liver against carbon tetrachloride (CCl4; an environmental pollutant)-induced lipid peroxidation and cell necrosis by blocking CYP2E1-mediated CCL4 metabolic activation and by upregulating Nrf2 downstream genes for NQO-1, HO-1, GCL, GST, and superoxide dismutase (SOD1).

Induction of cell cycle arrest

In normal cells, the cell cycle is tightly regulated to ensure faithful DNA replication and chromosomal segregation prior to cell division. When defects occur during DNA replication or chromosomal segregation and in case of DNA damage, the cell cycle can be transiently arrested at check points to allow for repair. Apoptosis is triggered when repair fails. Defective check points and evasion of apoptosis allow the unregulated division of cancer cells. Organosulfur compounds, including allicin, DAS, DADS, DATS, ajoene, and SAMC, have been found to induce cell cycle arrest when added to cancer cells in cell culture experiments. DATS reduced the incidence of poorly differentiated prostate tumors and limited the number of metastatic lesions in the lungs of mice genetically modified to develop prostate adenocarcinomas. DATS was shown to inhibit cancer cell proliferation, as well as neuroendocrine differentiation — a hallmark of prostate cancer malignancy — but had no effect on apoptosis and markers of invasion.In a rat model of chemically induced colon cancer, inhibition of cell proliferation by aged garlic extract was associated with a reduction in the incidence of precancerous lesions and dysplastic adenomas, but not of adenocarcinomas.

Induction of apoptosis

Apoptosis is a physiological process of programmed death of cells that are genetically damaged or no longer necessary. Precancerous and cancerous cells are resistant to signals that induce apoptosis. Garlic-derived organosulfur compounds, including allicin, ajoene, DAS, DADS, DATS, and SAMC, have been found to induce apoptosis when added to various cancer cell lines grown in culture. Oral administration of aqueous garlic extract and S-allylcysteine has been reported to enhance apoptosis in an animal model of oral cancer. Garlic oil reduced the incidence of N-nitrosodiethylamine-induced liver nodules by preventing oxidative damage to lipids and DNA and by promoting apoptosis. Garlic oil upregulated the activity of various antioxidant enzymes and expression of pro-apoptotic effectors like Bax and Caspase-3 and downregulated the expression of the anti-apoptotic genes β-arrestin-2, Bcl-2, and Bcl-X.

Inhibition of angiogenesis

To fuel their rapid growth, invasive tumors must develop new blood vessels by a process known as angiogenesis. Anti-angiogenic properties of several organosulfur compounds, including alliin, DATS, and ajoene, have been observed in in vitro or ex vivo experiments. In human breast cancer cells, DADS inhibited TNF-α-induced release of MCP-1, a chemokine that promotes tissue remodeling, angiogenesis, and metastasis. Aged garlic extract was also found to suppress in vitro angiogenesis by inhibiting endothelial cell proliferation, loss of adhesion, motility, and tube formation.

 

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