Garlic-derived natural polysulfanes as hydrogen sulfide donors: Friend or foe?

In vitro and in vivo studies reported the anti-cancer potential of organosulfur compounds (OSCs) as they trigger biological effects leading to cell cycle arrest with accumulation of cells in G2/M, alteration of the microtubular network, modulation of Bcl-2 family protein expression patterns and changes of the redox status. Despite these well-described effects, no OSC derivative is yet undergoing clinical trials even though their chemistry is well understood as OSCs act as hydrogen sulfide (H₂S) donors. H₂S is a biological mediator, synthesized through cysteine degradation and modulates vasodilation, cytoprotection, inflammation and angiogenesis. It is well accepted that H₂S plays a biphasic pharmacological role: the inhibition of endogenous synthesis of H₂S and paradoxically also the use of H₂S donors to increase H₂S concentration, induce both anti-cancer effects leading therefore to controversial discussions. Altogether, the role of H₂S in the anti-cancer action of OSCs remains poorly understood. In this review, we hypothesize that OSCs act through H₂S signaling pathways in cancer cells, and that a clearer understanding of the mechanism of action of H₂S in OSC-mediated anti-cancer activity is required for further application of these compounds in translational medicine.