Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis.

摘要: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a promising candidate for cancer therapy, however, emergence of drug resistance limits its potential use. Here, we report the first time that epigallocatechin-3-gallate (EGCG), major polyphenolic constituent green tea, sensitizes TRAIL-resistant LNCaP cells to TRAIL-mediated apoptosis through modulation intrinsic and extrinsic apoptotic pathways. When combined with EGCG, Apo2L/TRAIL exhibited enhanced activity in characterized by three molecular events. First, induction was accompanied upregulation poly(ADP-ribose) polymerase cleavage pro- antiapoptotic Bcl2 family proteins. A synergistic inhibition inhibitors concomitant increase caspase observed. Second, pretreatment EGCG resulted death-inducing signaling cascade complex involving DR4/TRAIL R1, Fas-associated death domain FLICE-inhibitory protein Last, observed invasion migration cells. This effect be mediated expression vascular endothelial growth factor, uPA angiopoietin 1 2. Further, MMP-2, -3 -9 TIMP1 treated combination TRAIL These data might have implications developing new strategies aimed at eliminating prostate resistant TRAIL.