|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21
Wen‑Jie Cai*1, Ming‑Jie Wang†, Li‑Hua Ju*, Cheng Wang* and Yi‑Chun Zhu†
*Department of Basic Medicine, University of Shanghai for Science and Technology, Shanghai 200093, Peoples Republic of China, and †Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, Peoples Republic of China
H2S (hydrogen sulfide), regarded as the third gaseous transmitter, is implicated in ulcerative colitis and colorectal cancers. The present study investigates the effects of H2S on cell proliferation in human colon cancer HCT 116 cells and SW480 cells. We identified the two key enzymes, CBS and CSE, for H2S synthesis in HCT 116 cells. An exogenously administered H2S donor NaHS induced cell proliferation in a concentration-dependent manner, with optimal proliferative concentration at 200 μmol/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 G0–G1 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 p21Waf1/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 p21Waf1/Cip1 expression and NO production. The results suggested a role for H2S in human colonic cancer development.
Key words: apoptosis, cell cycle, cell proliferation, hydrogen sulfide, nitric oxide
Abbreviations: BrdU, 5-bromo-2′-deoxyuridine, CBS, cystathionine β-synthase, CSE, cystathionine γ-lyase, ERK, extracellular-signal-regulated kinase, FBS, fetal bovine serum, GI tract, gastrointestinal tract, H2S, hydrogen sulfide, NO, nitric oxide, NOx, nitrate/nitrite, PI3K, phosphoinositide 3-kinase, PCNA, proliferating-cell nuclear antigen, TUNEL, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling, WST-8, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt
1To whom correspondence should be addressed (email email@example.com).
Received 31 October 2009/10 February 2010; accepted 25 February 2010
Published as Cell Biology International Immediate Publication 25 February 2010, doi:10.1042/CBI20090368
© 2010 The Author(s) Journal compilation © 2010 Portland Press Ltd