Role of H2S Donors in Cancer Biology

Abstract

Hydrogen sulfide (H2S) donors including organosulfur compounds (OSC), inorganic sulfide salts, and synthetic compounds are useful tools in studies to elucidate the effects of H2S in cancer biology. Studies using such donors have shown the ability of H2S to suppress tumor growth both in vitro and in vivo, with some of them suggesting the selectivity of its cytotoxic effects to cancer cells. In addition to promoting cancer cell death, H2S donors were also found to inhibit cancer angiogenesis and metastasis. The underlying mechanisms for the anticancer activities of H2S involve (1) cell signaling pathways, such as MAPK and STAT; (2) cell cycle regulation; (3) microRNAs regulation; and (4) cancer metabolism and pH regulation. Altogether, compiling evidences have demonstrated the great potential of using H2S donors as anticancer agents. Nevertheless, the application and development of H2S for therapy are still facing challenges as identification of molecular targets of H2S awaits further investigation.

Role of hydrogen sulfide donors in cancer development and progression

“…To date, numerous H 2 S releasing drugs with different properties, donating mechanisms, and capabilities have been synthesized for experimental use. With the exception of their molecular targets, the anti-cancer effects of H 2 S donors have been extensively reviewed [26][27][28][29]. Herein, we will summarize recent findings on the roles of H 2 S donors in cancer management by illuminating their molecular targets, mechanisms involved and their downstream effects in cellular activities.…”

I157172, a novel inhibitor of cystathionine γ-lyase, inhibits growth and migration of breast cancer cells via SIRT1-mediated deacetylation of STAT3

“…These data further confirmed the roles of the CSE/H 2 S system in deacetylation of STAT3 via SIRT1 in promoting breast cancer progression, and indicated that I157172 promoted SIRT1-mediated deacetylation of STAT3 in breast cancer cells and consequently inhibited the growth of breast cancer cells. Discussion H 2 S serves important roles in cancer cells (8,9) alongside its physiological functions in normal somatic cells (27). The effects of exogenous H 2 S on cancer cells differ from those of endogenous H 2 S. Several H 2 S donors exert therapeutic effects on cancer cells (27), whereas endogenous H 2 S may promote the proliferation of some cancer cells (4,8,9).…”

“…Discussion H 2 S serves important roles in cancer cells (8,9) alongside its physiological functions in normal somatic cells (27). The effects of exogenous H 2 S on cancer cells differ from those of endogenous H 2 S. Several H 2 S donors exert therapeutic effects on cancer cells (27), whereas endogenous H 2 S may promote the proliferation of some cancer cells (4,8,9). CSE, which is an endogenous H 2 S synthase, is a pyridoxal-5'-phosphate-dependent enzyme that catalyzes L-cysteine to yield H 2 S (28,29).…”

Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway

“…In the liver, H 2 S can be catalyzed by both cystathionine b-synthase (CBS) and cystathionine g-lyase (CSE) (23). Accumulating studies have demonstrated that H 2 S is involved in the pathophysiological progression of tumors (24)(25)(26)(27). However, the potential mechanism of H 2 S in cancer is unclear and controversial.…”