Inhibition of bcl-x(l) phosphorylation by tea polyphenols or epigallocatechin-3-gallate is associated with prostate cancer cell apoptosis.
Mol Pharmacol 2002 Oct;62(4):765-71
Kazi A; Smith DM; Zhong Q; Dou QP
Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
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.