Anti-cancer activity of new designer hydrogen sulfide-donating hybrids.

SIGNIFICANCE: Hydrogen sulfide (H2S) is likely to join nitric oxide (NO) and carbon monoxide (CO) as the third gaseous transmitter, influencing an array of intracellular signaling cascades. Thus, H2S is implicated in numerous physiological processes and in the pathology of various diseases. RECENT ADVANCES: H2S-donating agents that liberate H2S slowly either alone or in combination with NO, the so-called NOSH compounds, are being synthesized, and these have been shown to have great potential against cancer. CRITICAL ISSUES: An accurate determination of H2S levels is challenging. H2S and NO share many similar actions; do these similarities act to potentiate each other? Since many actions of H2S appear to be mediated through inhibition of inflammation and Nuclear factor kappa-light-chain-enhancer of activated B cells is a central player in this scenario, does S-nitrosylation of this transcription factor by NO affect its S-sulfhydration by H2S and vice versa? FUTURE DIRECTIONS: Deciphering the molecular targets of these novel hybrid agents and having genetically engineered animals should help us move toward targeted therapeutic applications. Human safety data with these new hybrids is essential.