Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21

Cell Biol Int. 2010 Apr 14;34(6):565-72. doi: 10.1042/CBI20090368.


H(2)S (hydrogen sulfide), regarded as the third gaseous transmitter, is implicated in ulcerative colitis and colorectal cancers. The present study investigates the effects of H(2)S on cell proliferation in human colon cancer HCT 116 cells and SW480 cells. We identified the two key enzymes, CBS and CSE, for H(2)S synthesis in HCT 116 cells. An exogenously administered H(2)S donor NaHS induced cell proliferation in a concentration-dependent manner, with optimal proliferative concentration at 200 micromol/l. NaHS administration increased Akt and ERK phosphorylation. Blockade of Akt and ERK activation attenuated NaHS-induced cell proliferation. Cell-cycle analysis showed that NaHS treatment for 6 h decreased the proportion of cells in G(0)-G(1) phase and increased the proportion of cells in S phase. Protein expressions of Cyclin D1 and PCNA (proliferating cell nuclear antigen) were not altered, but the cyclin-dependent kinase inhibitor p21(Waf1/Cip1) was inhibited significantly by NaHS treatment. NaHS significantly reduced NO metabolite levels. In conclusion, NaHS induced human colon cancer cell proliferation. This effect might be mediated by the increase of Akt and ERK phosphorylation and the decrease of p21(Waf1/Cip1) expression and NO production. The results suggested a role for H(2)S in human colonic cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / metabolism
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / physiology
  • Cystathionine beta-Synthase / genetics
  • Cystathionine beta-Synthase / metabolism
  • Cystathionine gamma-Lyase / genetics
  • Cystathionine gamma-Lyase / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • HCT116 Cells
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Nitric Oxide / metabolism
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-akt / physiology
  • Resting Phase, Cell Cycle
  • S Phase
  • Signal Transduction
  • Sulfides / chemistry
  • Sulfides / pharmacology


  • Cyclin-Dependent Kinase Inhibitor p21
  • Proliferating Cell Nuclear Antigen
  • Sulfides
  • Cyclin D1
  • Nitric Oxide
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Cystathionine beta-Synthase
  • Cystathionine gamma-Lyase
  • sodium bisulfide
  • Hydrogen Sulfide