P18 Effects of hydrogen sulfide on cancer cell growth and metastasis

Abstract

Many disparate studies have reported the ambiguous role of hydrogen sulfide (H 2 S) in cell survival. In our present study, cancer and non-cancer cells were exposed to H 2 S (using sodium hydrosulfide, NaHS and GYY4137) and cell viability was examined by crystal violet assay. High concentrations of continual H 2 S exposure decreased cell viability regardless of cancer or non-cancer cell types. However, continual but not single exposure to low concentration of H 2 S decreased cell viability more prominently in cancer, as compared to non-cancer cells. This suggested that low and continual exposure to H 2 S potentially serves as a novel and selective anti-cancer strategy. We then utilized GYY4137 as slow-H 2 S donor and identified that prolonged H 2 S exposure induced a significant intracellular acidification in cancer cells. Over-acidified intracellular environment eventually drove cancer cells to death. By contrast, no significant intracellular acidification was observed in non-cancer cells. Furthermore, we characterized that the anti-cancer activity of H 2 S was correlated with the aggressiveness of the cancer cell lines. This was in line with the magnitude of H 2 S-induced intracellular acidification. Synergistic anti-cancer effects of H 2 S and other compounds were investigated using highly invasive and chemoresistant cancer cell line models. On the other hand, we also examined the potential of using H 2 S donor GYY4137 to inhibit cancer metastasis. Taken together, H 2 S exhibits great potential to act as an anti-cancer therapeutic agent.