Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate
Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate
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DOI：
10.1006/bbrc.2000.3297
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发表时间：
2000-08-28
影响因子：
3.1
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Ahmad, N;Cheng, PY;Mukhtar, H
流行病学、体外细胞培养和体外动物研究表明，绿色茶或其组分多酚，特别是其主要多酚表没食子儿茶素-3-没食子酸酯（EGCG）可以预防许多癌症类型。在早期的研究中，我们发现绿色茶多酚EGCG导致人表皮样癌（A431）细胞的G 0/G1期细胞周期阻滞和凋亡。我们还证明，这些影响的表没食子儿茶素没食子酸酯可能介导的抑制核因子κ B，已与细胞周期调控和癌症。在这项研究中，采用A431细胞，我们提供的证据参与细胞周期蛋白激酶抑制剂（cki）-细胞周期蛋白依赖性激酶（cdk）机制在细胞周期失调的EGCG。免疫印迹分析表明，EGCG;细胞的处理导致显著的剂量和时间依赖性（i）WAF 1/p21、KIP 1/p27、p16和p18的蛋白表达上调，（ii）细胞周期蛋白D1、cdk 4和cdk 6的蛋白表达下调，但细胞周期蛋白E和cdk 2的蛋白表达不下调，（iii）与细胞周期蛋白E、细胞周期蛋白D1相关的激酶活性抑制，CDK 2、CDK 4和CDK 6。综上所述，我们的研究表明，EGCG引起G1期ckis的诱导，其抑制细胞周期的G 0/G1期中起作用的细胞周期蛋白-cdk复合物，从而引起细胞周期的G 0/G1期停滞，这是最终导致凋亡性细胞死亡的不可逆过程。我们认为，天然存在的药物，如绿色茶多酚，可以抑制细胞周期的进展，可以开发为有效的抗癌药物的癌症管理。(C)北京大学出版社.
Epidemiological, in vitro cell culture, and in vitro animal studies have shown that green tea or its constituent polyphenols, particularly its major polyphenol epigallocatechin-3-gallate (EGCG) may protect against many cancer types. In earlier studies, we showed that green tea polyphenol EGCG causes a G0/G1-phase cell cycle arrest and apoptosis of human epidermoid carcinoma (A431) cells. We also demonstrated that these effects of EGCG may be mediated through the inhibition of nuclear factor kappa B that has been associated with cell cycle regulation and cancer. In this study, employing A431 cells, we provide evidence for the involvement of cyclin kinase inhibitor (cki)-cyclin-cyclin-dependent kinase (cdk) machinery during cell cycle deregulation by EGCG. As shown by immunoblot analysis, EGCG; treatment of the cells resulted in significant dose- and time-dependent (i) upregulation of the protein expression of WAF1/p21, KIP1/p27, p16 and p18, (ii) downmodulation of the protein expression of cyclin D1, cdk4 and cdk6, but not of cyclin E and cdk2, (iii) inhibition of the kinase activities associated with cyclin E, cyclin D1, cdk2, cdk4 and cdk6. Taken together, our study suggests that EGCG causes an induction of G1-phase ckis, which inhibit the cyclin-cdk complexes operative in G0/G1 phase of the cell cycle thereby causing a G0/G1-phase arrest of the cell cycle, which is an irreversible process ultimately resulting in an apoptotic cell death. We suggest that the naturally occurring agents such as green tea polyphenols which may inhibit cell cycle progression could be developed as potent anticancer agents for the management of cancer. (C) 2000 Academic Press.