Hydrogen Sulfide Promotes Proliferation of HT-29 Colon Cancer Cells in a Mitochondria-independent Pathway

Abstract

Several studies reported the carcinogenic and anticarcinogenic effects of hydrogen sulfide. The present study evaluated the role of mitochondria in mediating the anti/pro-carcinogenic effect of hydrogen sulfide on colon cancer cells as mitochondrial KATP channel and mitochondrial electron transport chain are one of the promising targets for cancer treatment. The colon adenoma cell line and normal small intestinal epithelial cell lines were used to study the antiproliferative effect of hydrogen sulfide in the presence of enzyme inhibitors, mitochondrial KATP channel modulators and in presence of inhibitors of endogenous H2S metabolizing enzymes namely cystathionine-β-synthase and cystathionine-γ-lyase. Antiproliferative effect of hydrogen sulfide was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, crystal violet, sulforhodamine B and lactate dehydrogenase assays with its donor sodium hydrogen sulfide in both HT-29 and IEC-6 cells, where only IEC-6 cells showed significant cytotoxic effect at a concentration of 49.88 µg (IC50) but HT-29 failed to exhibit cytotoxicity with the same H2S concentration. In order to identify the mitochondrial role, several electron transporting chain inhibitors and KATP channel modulators were used, but still H2S could able to enhance the colon adenoma cell line growth indicating mitochondrial in-dependency in the pro-carcinogenic effect. However, anticarcinogenic effect of hydrogen sulfide was observed only when the cells were incubated in the presence of cystathionine-β-synthase and cystathionine-γ-lyase inhibitor, indicating their influential role in determining the exogenous hydrogen sulfide toxicity in colon adenoma cell line cells.