Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent inducer of p53-dependent apoptosis in the human lung cancer cell line A549
Identification of epigallocatechin-3-gallate in green tea polyphenols as a potent inducer of p53-dependent apoptosis in the human lung cancer cell line A549
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DOI：
10.1016/j.tiv.2009.04.011
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发表时间：
2009-08-01
影响因子：
3.2
通讯作者：
Yoshida, Kenichi
中科院分区：
文献类型：
--
作者：
Yamauchi, Rieko;Sasaki, Kaori;Yoshida, Kenichi
绿茶多酚对体外培养的癌细胞的作用已有较好的研究，尤其是表没食子儿茶素没食子酸酯(EGCG)的作用，因为表没食子儿茶素没食子酸酯(EGCG)通过调节细胞周期相关蛋白抑制肿瘤信号通路，诱导细胞周期停滞或凋亡。在本研究中，我们试图确定绿茶多酚(包括表儿茶素(EC)、表没食子儿茶素没食子酸酯(CG)、表没食子儿茶素(ECC)和EGCG)中每种或多种绿茶多酚调控的信号通路或靶分子。除EGCG外，心电、EGC和儿茶素混合物还显著降低细胞存活率。相反，caspase3/7活性是细胞凋亡的指标。是由EGCG特异性诱导的。通过进行一系列基于荧光素酶的报告分析，我们发现儿茶素混合物只上调P53报告。EGCG是一种更有效的P53依赖转录诱导剂，P53蛋白的诱导水平进一步支持了这一诱导作用。RNA干扰(RNAi)介导的p53基因敲除可完全阻断EGCG诱导的细胞凋亡。最后，使用大约70种不同抗体的蛋白质组和蛋白质印迹分析未能检测到儿茶素混合物处理的A549细胞中上调的蛋白质。综上所述，这些结果表明，在几种绿茶多酚中，EGCG是一种有效的凋亡诱导剂，其功能仅通过A549细胞中依赖于P53的途径发挥作用。(C)2009爱思唯尔有限公司。保留所有权利。
The effects of green tea polyphenols on cultured cancer cells have been well characterized, especially the effects of epigallocatechin-3-gallate (EGCg), since EGCg suppresses oncogenic signaling pathways and induces cell cycle arrest or apoptosis by regulating cell cycle-associated proteins. In the present study, we attempted to identify signaling pathways or target molecules regulated by each of or a mixture of green tea polyphenols, including epicatechin (EC), epicatechin-3-gallate (ECg), epigallocatechin (ECC), and EGCg, in the human lung cancer cell line A549. ECg, EGC, and a catechin mixture, in addition to EGCg, significantly decreased cell viability. In contrast, caspase 3/7 activity, an apoptosis indicator. was specifically induced by EGCg. By conducting a series of luciferase-based reporter assays, we revealed that the catechin mixture only up-regulates the p53 reporter. EGCg was a more potent inducer of p53-dependent transcription, and this induction was further supported by the induced level of p53 protein. RNA interference (RNAi)-mediated p53 knockdown completely abolished EGCg-induced apoptosis. Finally, a proteome and western blot analysis using approximately 70 different antibodies failed to detect up-regulated proteins in catechin mixture-treated A549 cells. Taken together, these results indicate that EGCg, among several green tea polyphenols, is a potent apoptosis inducer that functions exclusively through a p53-dependent pathway in A549 cells. (C) 2009 Elsevier Ltd. All rights reserved.