Document Detail

Genistein induces p21(Cip1/WAF1) expression and blocks the G1 to S phase transition in mouse fibroblast and melanoma cells.
MedLine Citation:
PMID:  9790949     Owner:  NLM     Status:  MEDLINE    
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.
T Kuzumaki; T Kobayashi; K Ishikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  251     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-11-23     Completed Date:  1998-11-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  291-5     Citation Subset:  IM    
Copyright Information:
Copyright 1998 Academic Press.
Department of Biochemistry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
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MeSH Terms
3T3 Cells
Cells, Cultured
Cyclin E
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases / antagonists & inhibitors
Cyclins / biosynthesis*
G1 Phase / drug effects*
Genistein / pharmacology*
Growth Inhibitors / pharmacology*
Melanoma / metabolism*
Mice, Inbred BALB C
Plant Extracts / pharmacology
S Phase / drug effects*
Tumor Cells, Cultured
Reg. No./Substance:
0/Cdkn1a protein, mouse; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Growth Inhibitors; 0/Plant Extracts; 446-72-0/Genistein; EC Kinases

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