Butyrate-stimulated H2S Production in Colon Cancer Cells

Butyrate is a short-chain fatty acid that arrests growth of various types of cells. H2S can be endogenously produced by cystathionine g-lyase (CSE) or cystathionine beta-synthase (CBS) or both in colonic tissues. In this study, we observed endogenous H2S production in a colon cancer cell line (WiDr) and colonic tissues through the activity of both CSE and CBS. After 24 h of incubation of WiDr cells, butyrate increased cell production of H2S and upregulated CBS and CSE expressions. Both butyrate and NaHS (a H2S donor) decreased cell viability in a dose-dependent manner. Blockade of CBS, but not CSE, decreased butyrate-stimulated H2S production and reversed butyrate-inhibited cell viability. In addition, NaHS treatment stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase (JNK). Inhibition of the phosphorylation of either p38 MAPK or ERK did not abolish NaHS-induced cell death. Butyrate treatment increased the phosphorylation of ERK, not p38 MAPK and JNK, but inhibition of ERK and p38 MAPK phosphorylation did not inhibit butyrate-reduced cell viability. In conclusion, butyrate regulates endogenous H2S production by stimulating CBS expression in colon cancer cells, but butyrate and H2S inhibit cancer cell growth through different mechanisms. Antioxid. Redox Signal. 12, 1101-1109.