Vol. 62, Issue 4, 765-771, October 2002

ACCELERATED COMMUNICATION
Inhibition of Bcl-X_L Phosphorylation by Tea Polyphenols or Epigallocatechin-3-Gallate Is Associated with Prostate Cancer Cell Apoptosis

Aslamuzzaman Kazi, David M. Smith, Qing Zhong, and Q. Ping Dou

Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute (A.K., D.M.S., Q.Z., Q.P.D.), and Departments of Interdisciplinary Oncology (A.K., Q.Z., Q.P.D.) and Biochemistry & Molecular Biology (D.M.S., Q.P.D.), College of Medicine, University of South Florida, Tampa, Florida

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.