Resveratrol sensitizes androgen independent prostate cancer cells to death-receptor mediated apoptosis through multiple mechanisms

摘要: BACKGROUND A critical factor in prostate cancer development and progression is the altered expression of apoptotic regulatory proteins which renders cells resistant to both hormone- chemo-therapies. Resveratrol, a dietary component with chemopreventive properties has been reported resensitize variety cell types apoptosis. In current study, ability resveratrol pre-treatment sensitize hormone refractory lines (PC-3 DU145) apoptosis mechanisms involved were investigated. METHODS Apoptosis was assessed using several established parameters protein analyzed by Western blot flow cytometry. IAP knockdown achieved RNAi while inhibition Akt phosphorylation pre-incubation PI3-kinase inhibitor LY294002. RESULTS Pre-treatment sensitized PC-3 DU145 agents that specifically target death receptors (TRAIL, Fas, TNFα) but not initiate through other (Etoposide, Paclitaxel, Tunicamycin, Thapsigargin). Resveratrol IAPs Bax, decreased cells, leading increased caspase activation While siRNA did mimic effects resveratrol, LY294002 TRAIL induced etoposide or tunicamycin. CONCLUSION Altering susceptibility advanced androgen independent disease requires manipulation broad signaling pathway. Use may represent an important therapeutic approach combination conventional therapies for treatment cancer. Prostate 67: 1641–1653, 2007. © 2007 Wiley-Liss, Inc.