Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation
Epigallocatechin-3-gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation
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DOI：
10.1016/j.cbi.2007.09.001
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发表时间：
2008-01-10
影响因子：
5.1
通讯作者：
Bomser, Joshua A.
中科院分区：
文献类型：
--
作者：
Albrecht, Daniel S.;Clubbs, Elizabeth A.;Bomser, Joshua A.
表没食子儿茶素-3-没食子酸酯（EGCG），一种茶多酚，抑制许多癌细胞系的增殖；然而，其抗增殖机制尚不明确。本研究的目的是确定EGCG在PC-3前列腺癌细胞系中抗增殖作用的细胞信号传导机制。EGCG抑制PC-3细胞增殖呈浓度依赖性，IC50值为39.0 μ M，但对非致瘤性前列腺上皮细胞系（RWPE-1）的增殖无影响。EGCG （0-50 μ M）处理PC-3细胞导致细胞外信号调节激酶（ERK1/2）通路的时间和浓度依赖性激活。EGCG处理未诱导RWPE-1细胞的ERK1/2活性。PD98059不抑制EGCG对ERK1/2的激活，PD98059是一种有效的丝裂原活化蛋白激酶（MEK）抑制剂，MEK是ERK1/2激活的直接上游激酶；提示与mek无关的信号机制。磷酸甘氨酸-3激酶（PI3K）抑制剂预处理PC-3细胞部分降低了egcg诱导的ERK1/2激活和这种多酚的抗增殖作用。这些结果表明，通过mek不依赖、pi3 - k依赖的信号通路激活ERK1/2是EGCG在PC-3细胞中抗增殖作用的部分原因。2007爱思唯尔爱尔兰有限公司版权所有。
Epigallocatechin-3-gallate (EGCG), a tea polyphenol, inhibits the proliferation of many cancer cell lines; however, the antiproliferative mechanism(s) are not well-characterized. The objective of this study is to identify the cellular signaling mechanism(s) responsible for the anti proliferative effects of EGCG in the PC-3 prostate cancer cell line. EGCG inhibited PC-3 cell proliferation in a concentration-dependent manner with an IC50 value of 39.0 mu M, but had no effect on the proliferation of a nontumorigenic prostate epithelial cell line (RWPE-1). Treatment of PC-3 cells with EGCG (0-50 mu M) resulted in time and concentration-dependent activation of the extracellular signal-regulated kinase (ERK1/2) pathway. EGCG treatment did not induce ERK1/2 activity in RWPE-1 cells. The activation of ERK1/2 by EGCG was not inhibited using PD98059, a potent inhibitor of mitogen-activated protein kinase kinase (MEK), the immediate upstream kinase responsible for ERK1/2 activation; suggesting a MEK-independent signaling mechanism. Pretreatment of PC-3 cells with a phosphomositide-3 kinase (PI3K) inhibitor partially reduced both EGCG-induced ERK1/2 activation and the anti proliferative effects of this polyphenol. These results suggest that ERK1/2 activation via a MEK-independent, PI3-K-dependent signaling pathway is partially responsible for the anti proliferative effects of EGCG in PC-3 cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.