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KMID : 1140120060110040311
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Cancer Prevention Research
2006 Volume.11 No. 4 p.311 ~ p.320
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Induction of G2/M Arrest by Genistein in Human AGS Gastric Carcinoma and SK-MEL-2 Melanoma Cells
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Choi Woo-Yung
Park Cheol
Kim Kyung-Mi
Han Min-Ho
Choi Yung-Hyun
Lee Won-Ho
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Abstract
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Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation and chemopreventive effects. In the present study, we investigated the mechanism of action by which genistein suppressed the proliferation of AGS human gastric carcinoma and SK-MEL-2 melanoma cells. Treatment of AGS and SK-MEL-2 cells to genistein resulted in the growth inhibition and morphological change in a dose-dependent manner. Flow cytometric analysis revealed that genistein
treatment caused G2/M phase arrest of the cell cycle, which was associated with a down-regulation of cyclin A, cyclin B1 and cyclin-dependent kinase (Cdk) 2. And we also observed down-regulation of Cdc25C, which was a marker of cell proliferation, and plays important role in cyclin B-Cdc2 complex activation, however Wee1 kinase expression was not affected. Furthermore, genistein induced Cdk inhibitor p21 (WAF1/CIP1) expression through p53-independent manner in AGS cells, but not affect in SK-MEL-2 cells. Taken together, these data provide strong molecular evidence for the anti-tumor activity of genistein in AGS human gastric carcinoma and SK-MEL-2 melanoma cells.
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KEYWORD
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Genistein, AGS, SK-MEL-2, G2/M arrest, p21
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