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Publication : Genistein induces p21(Cip1/WAF1) expression and blocks the G1 to S phase transition in mouse fibroblast and melanoma cells.

First Author  Kuzumaki T Year  1998
Journal  Biochem Biophys Res Commun Volume  251
Issue  1 Pages  291-5
PubMed ID  9790949 Mgi Jnum  J:52740
Mgi Id  MGI:1330098 Doi  10.1006/bbrc.1998.9462
Citation  Kuzumaki T, et al. (1998) Genistein induces p21(Cip1/WAF1) expression and blocks the G1 to S phase transition in mouse fibroblast and melanoma cells. Biochem Biophys Res Commun 251(1):291-5
abstractText  Genistein, the principal isoflavonoid in soybeans, is reported to inhibit cell cycle progression, but the molecular basis for this event is unknown. Here we show that genistein inhibits DNA synthesis and suppresses cyclin E-associated cyclin-dependent kinase-2 (CDK2) activity when quiescent BALB/c 3T3 fibroblasts are stimulated with serum. In these cells, a CDK2 inhibitor, p21(Cip1/WAF1), is markedly increased by genistein, but another CDK2 inhibitor, p27(Kip1), is not increased. In exponentially growing BALB/c 3T3 cells, genistein inhibits proliferation of the cells in a dose-dependent manner. Flow cytometric analysis and measurement of DNA synthesis indicate that genistein blocks the G1 to S phase transition of these cells, which is concomitant with G2-M arrest. In mouse B16-F1 melanoma cells, genistein also blocks the transition of G1 to S phase without arresting at G2-M at low doses. In both cell lines, genistein suppresses cyclin E/CDK2 activity and induces p21(Cip1/WAF1) expression. These results suggest that genistein affects the restriction point control of the cell cycle by inducing p21(Cip1/WAF1) expression in mouse fibroblast and melanoma cells. Copyright 1998 Academic Press.
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