(-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells
(-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells
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DOI：
10.1016/j.cdp.2007.10.018
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Piva, Roberta
中科院分区：
文献类型：
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作者：
Farabegoli, Fulvia;Barbi, Cristiana;Piva, Roberta
背景：表没食子儿茶素没食子酸酯(EGCG)是绿茶中活性最强的儿茶素，具有化学预防和选择性杀伤癌细胞的作用。由于先前的研究发现儿茶素可以与17-β-雌二醇竞争与雌激素受体α(ERα)的结合，我们询问EGCG是否可以调节ERα的作用。方法：我们使用MCF-7，一种高水平表达ERA的乳腺癌细胞株。用不同浓度的EGCG处理细胞，用四甲基偶氮唑盐比色法检测细胞存活率。提取RNA后，用RT-PCR方法检测Era和PS2的表达。为了更好地确定EGCG的作用与ERα的关系，我们研究了EGCG对耐他莫昔芬的MCF-7细胞(MCF-7tam)、10(-7)M ICI 182,780处理8天的MCF-7细胞以及通过流式细胞仪(FCM)检测缺乏ERA的细胞株MDA-MB-231的细胞毒性。结果：低浓度的EGCG(30µg/ml)处理后，Era和PS2mRNA均有表达。在此浓度下，未检测到细胞变化。100mU g/mlEGCG作用24 h后，PS2表达缺失，提示Era发生改变。当ERA不存在(MDA-MB-231)或被他莫昔芬或ICI 182,780灭活时，EGCG的细胞毒性较低。结论：功能活性ER(X)可能参与了EGCG的细胞毒作用，增加了对药物的敏感性。由于较高的EGCG浓度也会杀死对他莫昔芬耐药的细胞或经10-7M ICI 182,780治疗的细胞，EGCG应该更好：在以类固醇受体为靶点的药物治疗的乳腺癌细胞中进行研究，作为治疗的潜在补充。(C)2007年国际预防肿瘤学学会。爱思唯尔有限公司出版。保留所有权利。
Background: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin present in green tea, demonstrated to have chemopreventive action and to kill cancer cells selectively. As a previous study found that catechins could compete with 17-beta-estradiol for binding to estrogen receptor alpha (ER alpha), we asked whether EGCG could regulate ER alpha action. Methods: We used MCF-7, a breast carcinoma cell line having a high level of ERa expression. The cells were treated with various EGCG concentrations and cell viability was evaluated by MTT assay. ERa and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ER alpha, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10(-7) M ICI 182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERa by flow cytometry (FCM). Results: Both ERa and pS2 mRNA were expressed in samples treated with low EGCG concentration (30 mu g/ml). At this concentration, no cell change was detectable. In contrast, pS2 expression was lost in samples treated with 100 mu g/ml EGCG for 24 h, indicating ERa alteration. EGCG cytotoxicity was lower when ERa was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 182,780). Conclusions: Functionally active ER(x may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher EGCG concentrations also killed cells resistant to tamoxifen or treated by 10-7 M ICI 182,780, EGCG ought to be better :investigated in breast carcinoma cells treated with drugs targeted to steroid receptors, as a potential complement of therapy. (C) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.