Hydrogen sulfide in cancer: Friend or foe?

• Hydrogen sulfide (H2S) has opposite effects on cancer: pro-cancer and anti-cancer.
• Endogenous H2S promotes cancer development and progression.
• Inhibition of endogenous H2S production may be a new strategy for cancer treatment.
• Relatively high concentration of exogenous H2S suppresses growth of cancer cells.
• H2S donors and H2S-releasing hybrids could be developed as novel anti-cancer drugs.

Hydrogen sulfide (H2S) is the third gaseous signaling molecule that plays important roles in cancer biological processes. Recent studies indicate that H2S has both pro-cancer and anti-cancer effects. Endogenous H2S can exert pro-cancer functions through induction of angiogenesis regulation of mitochondrial bioenergetics, acceleration of cell cycle progression, and anti-apoptosis mechanisms. Thus, the inhibition of the production of H2S in cancer cells may be a new cancer treatment strategy. In contrast to the pro-cancer effect of H2S, relatively high concentrations of exogenous H2S could suppress the growth of cancer cells by inducing uncontrolled intracellular acidification, inducing cell cycle arrest, and promoting apoptosis. Therefore, H2S donors and H2S-releasing hybrids could be designed and developed as novel anti-cancer drugs. In this review, the production and metabolism of H2S in cancer cells are summarized and the role and mechanism of H2S in cancer development and progression are further discussed.