s-allylcysteine and Neoplasms

The purpose of this review is to discuss the molecular mechanisms underlying the anticancer properties of S-allylcysteine (SAC). Over the decades, evidence derived from in vitro and in vivo studies has shown that this predominant organosulfur component of aged garlic extract has multiple anticancer properties; hence, some potential mechanisms responsible for the anticarcinogenic action have been suggested. These mechanisms include induction of carcinogen detoxification, inhibition of cell proliferation and growth, mediation of cell cycle arrest, induction of cell death, inhibition of epithelial-mesenchymal transition and cell invasion, suppression of metastasis, and induction of immunomodulation in cancer cells. However, the actions and mechanisms are not comprehensive, and important aspects of the anticancer activities of SAC still need to be explored. In light of the current evidence, more specific studies, specifically clinical and epidemiological, are required to advance the promising use of SAC as a chemopreventive and therapeutic agent in cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Cysteine; Disease Models, Animal; Garlic; Humans; Mice; Neoplasms; Rats

Topics: Allium; Animals; Anti-Infective Agents; Antineoplastic Agents; Blood Platelets; Cysteine; Disulfides; Fibrinolysis; Garlic; Humans; Immunologic Factors; Neoplasms; Obesity; Phytochemicals; Plant Extracts; Solubility; Sulfoxides; Sulfur; Sulfur Compounds

Metastatic cancer is one of the main causes of cancer-related death since they rarely respond to available treatments. Recently, certain compounds isolated from the dietary supplement, garlic, have shown anti-proliferation effect on cancer cells. The aim of this study was to investigate whether certain garlic derivatives had any effect on the potentially invasive androgen-independent prostate cancer (PCa) cells. Using colony-forming, wound-closure as well as matrigel-invasion assays, we found that two main water-soluble constituents of the garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), were able to suppress PCa cell proliferation and invasive abilities. This inhibitory effect was associated with induction of mesenchymal to epithelial transition. Most importantly, the SAC and SAMC treatment led to restoration of E-cadherin expression at transcription and protein levels. In contrast, the expression of E-cadherin repressor, Snail, was reduced in the SAC- and SAMC-treated cells. Furthermore, examination of cell lines from other types of cancer (ovarian, nasopharyngeal and esophageal carcinomas) also confirmed that the effect of SAC and SAMC on activation of E-cadherin might be a general effect on human cancer cells. Our results demonstrate a novel anticancer effect of garlic and suggest that certain garlic-derived compounds may be potential agents for suppression of invasive growth through restoration of E-cadherin expression in cancer cells.

Topics: Antineoplastic Agents; Cadherins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen; Cysteine; Drug Combinations; Drug Design; Garlic; Humans; Inhibitory Concentration 50; Laminin; Neoplasm Invasiveness; Neoplasms; Proteoglycans

Topics: Antineoplastic Agents, Phytogenic; Cell Division; Cysteine; Garlic; Humans; Neoplasms; Plants, Medicinal

Diallyl disulfide (DADS), an oil-soluble organosulfur compound in processed garlic, was more effective in inhibiting the in vitro growth of human tumor cell lines: HCT-15 (colon), A549 (lung), and SK MEL-2 (skin) than isomolar quantities of the water-soluble compound S-allyl cysteine (SAC). Addition of DADS (100 microM) was cytostatic to all three cell lines. The importance of the allyl and the disulfide groups were revealed by the lack of a comparable depression in the growth of HCT-15 cells exposed to its saturated analogue, dipropyl disulfide (DPDS). Treatment with DADS also resulted in a dose-dependent increase in intracellular free calcium in cells. A dose-dependent decrease in the activity of calcium-dependent ATPase enzyme occurred in HCT-15 cells exposed to increasing quantities of DADS. A correlation (r = -0.975) was found between the intracellular free calcium levels and the Ca-ATPase activity in DADS-treated cells. These studies document that DADS, a constituent of garlic oil, is an effective inhibitor of the growth of human neoplastic cells. Alterations in calcium hemostasis are likely involved in the growth inhibition/cytotoxicity caused by DADS.

Topics: Allyl Compounds; Antineoplastic Agents; Calcium; Calcium-Transporting ATPases; Cell Division; Cysteine; Disulfides; Egtazic Acid; Ethylmaleimide; Garlic; Humans; Kinetics; Molecular Structure; Neoplasms; Plants, Medicinal; Tumor Cells, Cultured