Hydrogen sulfide induces human colon cancer cell proliferation: Role of Akt,ERK and p21 |
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Authors: | Wen‐Jie Cai Ming‐Jie Wang Li‐Hua Ju Cheng Wang Yi‐Chun Zhu |
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Institution: | 1. Department of Basic Medicine, University of Shanghai for Science and Technology, Shanghai 200093, Peoples Republic of China;2. Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, Peoples Republic of China |
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Abstract: | 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. |
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Keywords: | apoptosis cell cycle cell proliferation hydrogen sulfide nitric oxide |
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