Inhibition of Bcl-XL phosphorylation by tea polyphenols or epigallocatechin-3-gallate is associated with prostate cancer cell apoptosis

被引:33
作者
Kazi, A
Smith, DM
Zhong, Q
Dou, QP
机构
[1] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program,MRC 1259C, Tampa, FL 33612 USA
[2] Univ S Florida, Coll Med, Dept Interdisciplinary Oncol, Tampa, FL USA
[3] Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Tampa, FL USA
关键词
D O I
10.1124/mol.62.4.765
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Prostate cancer cells demonstrate slow growth kinetics and chemoresistance. Tea polyphenols have been shown to exert prostate cancer-preventative effects. Here we report that growth-arrested prostate cancer cells expressed high levels of a hyperphosphorylated Bcl-X-L in mitochondria. Treatment with tea polyphenols or the major tea component epigallocatechin-3-gallate blocked expression of the hyper-, but not hypophosphorylated Bcl-X-L in mitochondria, accompanied by cytochrome c release, caspase activation, and apoptosis. Studies using specific inhibitors suggest that tea inhibits p38 mitogen-activated protein kinase and the proteasome activities, leading to inhibition of Bcl-X-L phosphorylation and induction of prostate cancer cell death.
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收藏
页码:765 / 771
页数:7
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