Kuzumaki T, Kobayashi T, Ishikawa K
Department of Biochemistry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
Biochem Biophys Res Commun. 1998 Oct 9;251(1):291-5. doi: 10.1006/bbrc.1998.9462.
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.
染料木黄酮是大豆中的主要异黄酮，据报道它能抑制细胞周期进程，但其分子机制尚不清楚。在此我们表明，当用血清刺激静止的BALB/c 3T3成纤维细胞时，染料木黄酮可抑制DNA合成并抑制细胞周期蛋白E相关的细胞周期蛋白依赖性激酶2（CDK2）活性。在这些细胞中，染料木黄酮可使CDK2抑制剂p21（Cip1/WAF1）显著增加，但另一种CDK2抑制剂p27（Kip1）并未增加。在指数生长的BALB/c 3T3细胞中，染料木黄酮以剂量依赖的方式抑制细胞增殖。流式细胞术分析和DNA合成测量表明，染料木黄酮可阻断这些细胞从G1期到S期的转变，并伴有G2-M期阻滞。在小鼠B16-F1黑色素瘤细胞中，低剂量的染料木黄酮也可阻断G1期到S期的转变，但不会在G2-M期阻滞。在这两种细胞系中，染料木黄酮均抑制细胞周期蛋白E/CDK2活性并诱导p21（Cip1/WAF1）表达。这些结果表明，染料木黄酮通过在小鼠成纤维细胞和黑色素瘤细胞中诱导p21（Cip1/WAF1）表达来影响细胞周期的限制点控制。
