OP18 Utilization of hydrogen sulfide donor as a cancer therapy

Abstract

Very little is known regarding role of hydrogen sulfide (H2S) in cancer biology. We showed that slow H2S donor, GYY4137 [1] exhibited anti-cancer effect both in vitro and in vivo. Using conventional H2S detection method methylene blue assay, we demonstrated the different H2S-releasing manner of sodium hydrosulfide (NaHS) and GYY4137. NaHS releases H2S acutely and in high amount as contrast to GYY4137 which releases H2S slowly and in low yet detectable level. Surprisingly, anti-proliferative effect of H2S was observed across a broad range of cancer cell lines (HeLa, HCT-116, HepG2, U2OS, MCF7, HL-60 and MV4–11) in GYY4137 treatment but was of little effect or not significant in NaHS treatment. This suggested that prolonged exposure to low concentration of H2S may serve as novel anti-cancer strategy. Furthermore, normal cell lines (WI38 and IMR90) tested were not affected by GYY4137 nor NaHS. Tumor xenograft mice model too showed a significant shrinkage of tumor volume in a GYY4137 dose-dependent manner [2] . Further analysis on this selective phenomena suggested that H2S killing effect may be glucose metabolism related. We identified that H2S induced an altered glucose metabolism rate and interfered with pH homeostasis that led to significant pH disruption in cancer cells. This eventually drives cancer cells to death. On the other hand, pH of normal cells was not affected by H2S. Selectivity of H2S targeting on cancer but not normal cells would serve as a novel and effective cancer therapy.