Modulation of hydrogen sulfide gasotransmitter limits the proven benefits of garlic

Garlic has been used as a medicinal food for centuries. The biological activity of garlic relies on the presence of highly reactive sulfur compounds. Widespread in vitro and in vivo studies have reported the mechanism of action of the anticancer activity of garlic-derived organosulfur compounds (OSCs) in a wide range of cancer types. Moreover, epidemiological studies support an inverse correlation between garlic intake and cancer risk. More recently, several studies have reported the ability of garlic-derived OSCs to release hydrogen sulfide (H2S) and to affect H2S biosynthesis by altering specific H2S enzyme activity, such as cystathionine-beta-synthase or cystathionine-gamma-lyase. Paradoxically, some studies have reported that overexpression of H2S-producing enzymes is associated with ovarian and colon cancer progression. In this review, we aimed to provide a critical analysis of garlic anticancer activity by documenting our current understanding of the anticancer activity of garlic-derived OSCs. We propose here to raise a mechanistic gap in garlic-mediated anticancer activity by documenting our current knowledge of the role of H2S in cancer biology.