Inhibition of bcl-x(l) phosphorylation by tea polyphenols or epigallocatechin-3-gallate is associated with prostate cancer cell apoptosis.
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.
Kazi
Aslamuzzaman
A
Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
Smith
David M
DM
Zhong
Qing
Q
Dou
Q Ping
QP
D017209:Apoptosis; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D015536:Down-Regulation; D005419:Flavonoids; D015870:Gene Expression; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D011108:Polymers / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D019253:Proto-Oncogene Proteins c-bcl-2; D013662:Tea; D051020:bcl-X Protein; D002392:Catechin; C045651:epigallocatechin gallate