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Int J Biol Sci 2010; 6(7):784-795. doi:10.7150/ijbs.6.784

Research Paper

S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

Jin Luo1,*, Yan-Ni Li2,*, Fei Wang3,*, Wei-Ming Zhang1, Xin Geng1

1. Department of biochemistry, Tianjin Medical University, Tianjin, 300070 China
2. Tianjin Stomatological Hospital, Tianjin, China
3. Department of Neurology, General Hospital, Tianjin Medical University, Tianjin, 300052 China
* These authors contribute equally to this work.

Abstract

A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM) serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a), as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell growth in gastric cancer cells and colon cancer cells, and the inhibition efficiency was significantly higher than that in the normal cells. Under standard growth conditions, C-myc and H-ras promoters were hypomethylated in gastric cancer cells and colon cancer cells. SAM treatment resulted in a heavy methylation of these promoters, which consequently downregulated mRNA and protein levels. In contrast, there was no significant difference in mRNA and protein levels of p16 (INK4a) with and without SAM treatment. SAM can effectively inhibit the tumor cells growth by reversing the DNA hypomethylation on promoters of oncogenes, thus down-regulating their expression. With no influence on the expression of the tumor suppressor genes, such as P16, SAM could be used as a potential drug for cancer therapy.

Keywords: S-Adenosylmethionine, epigenetics, hypomethylation, gastric cancer, cancer therapy

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How to cite this article:
Luo J, Li YN, Wang F, Zhang WM, Geng X. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer. Int J Biol Sci 2010; 6(7):784-795. doi:10.7150/ijbs.6.784. Available from http://www.ijbs.com/v06p0784.htm