Butyrate-stimulated H2S production in colon cancer cells

Antioxid Redox Signal. 2010 May 1;12(9):1101-9. doi: 10.1089/ars.2009.2915.


Butyrate is a short-chain fatty acid that arrests growth of various types of cells. H(2)S can be endogenously produced by cystathionine gamma-lyase (CSE) or cystathionine beta-synthase (CBS) or both in colonic tissues. In this study, we observed endogenous H(2)S 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 H(2)S and upregulated CBS and CSE expressions. Both butyrate and NaHS (a H(2)S donor) decreased cell viability in a dose-dependent manner. Blockade of CBS, but not CSE, decreased butyrate-stimulated H(2)S 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 H(2)S production by stimulating CBS expression in colon cancer cells, but butyrate and H(2)S inhibit cancer cell growth through different mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyrates / pharmacology*
  • Cell Line, Tumor
  • Cell Survival
  • Colonic Neoplasms / metabolism*
  • Cystathionine beta-Synthase / metabolism
  • Cystathionine gamma-Lyase / metabolism
  • Humans
  • Hydrogen Sulfide / chemistry
  • Hydrogen Sulfide / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / metabolism
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Butyrates
  • RNA, Small Interfering
  • p38 Mitogen-Activated Protein Kinases
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • Hydrogen Sulfide