Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules
Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules
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DOI：
10.1016/s0014-2999(01)01144-x
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发表时间：
2001-08-17
影响因子：
5
通讯作者：
Chou, CJ
中科院分区：
文献类型：
--
作者：
Hsu, SL;Hsieh, YC;Chou, CJ
黄芩素是一种存在于黄芩根中的黄酮类化合物，据报道可抑制几种类型细胞的细胞增殖。本研究以原代培养的大鼠心脏内皮细胞为模型，探讨黄芩素对内皮细胞生长的影响及其作用机制。在这里，我们报告说，治疗与100 μ M黄芩素引起了几乎完全抑制细胞增殖后，5天的孵育。黄芩素介导的G1和G2期生长阻滞伴随着细胞周期蛋白D2、细胞周期蛋白A、细胞周期蛋白依赖性激酶1（Cdk-1）和细胞周期蛋白依赖性激酶2（Cdk-2）的下调以及p15（Ink 4 B）、p21（CIP 1/Waf 1）、p53和细胞周期蛋白E的上调。对细胞周期蛋白-Cdk复合物激酶活性的评估表明，黄芩素降低了内皮细胞中Cdk 1、Cdk 2、细胞周期蛋白D2和细胞周期蛋白A的表达，导致Cdk/细胞周期蛋白相关激酶活性显著降低。结果提示，黄芩素抑制大鼠心脏内皮细胞增殖，其机制可能与抑制Cdk 1、Cdk 2、cyclin D2和cyclin A蛋白的表达和功能，上调cyclin E、p15（Ink 4 B）、p53和p21（CIP 1/Waf 1）有关。(C)2001爱思唯尔科技有限公司。保留所有权利。
Baicalein, a flavonoid present in the root of Scutellaria baicalensis Georgi, has been reported to inhibit cell proliferation in several types of cells. In this study, the effect of baicalein on cell growth and the mechanism of growth modulation were examined in primary cultured rat heart endothelial cells. Here, we report that treatment with 100-muM baicalein caused an almost complete inhibition of cell proliferation after 5 days of incubation. Baicalein mediated G1 and G2 growth arrest accompanied by the down-regulation of cyclin D2, cyclin A, cyclin-dependent kinase 1 (Cdk-1) and cyclin-dependent kinase 2 (Cdk2), and up-regulation of p15(Ink4B), p21(CIP1/Waf1), p53 and cyclin E. Evaluation of the kinase activity of cyclin-Cdk complexes showed that baicalein decreased Cdk1, Cdk2, cyclin D2 and cyclin A expression in endothelial cells, leading to markedly reduced Cdk/cyclin-associated kinase activities. These results suggest that baicalein inhibits the proliferation of rat heart endothelial cells via G1 and G2 arrest in association with the down-regulation of the expression and function of Cdk1, Cdk2, cyclin D2 and cyclin A proteins, and up-regulation of cyclin E, p15(Ink4B), p53 and p21(CIP1/Waf1). (C) 2001 Elsevier Science B.V. All rights reserved.