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Hydrogen sulfide induces human colon cancer cell proliferation: Role of Akt, ERK and p21
Author(s) -
Cai WenJie,
Wang MingJie,
Ju LiHua,
Wang Cheng,
Zhu YiChun
Publication year - 2010
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20090368
Subject(s) - cell growth , protein kinase b , mapk/erk pathway , cyclin d1 , chemistry , pi3k/akt/mtor pathway , cancer research , cell cycle , proliferating cell nuclear antigen , kinase , cell , microbiology and biotechnology , phosphorylation , signal transduction , biology , biochemistry
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 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 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.