TY - JOUR T1 - Synergistic Cell Death by EGCG and Ibuprofen in DU-145 Prostate Cancer Cell Line JF - Anticancer Research JO - Anticancer Res SP - 3947 LP - 3956 VL - 27 IS - 6B AU - MYOUNG H. KIM AU - JAEGWON CHUNG Y1 - 2007/11/01 UR - http://ar.iiarjournals.org/content/27/6B/3947.abstract N2 - Background: One of the green tea components epigallocatechin-3-gallate (EGCG) significantly prevented the growth of prostate cancer cells. In this study, synergistic effect of EGCG and ibuprofen (EGCG+ibuprofen) was investigated to determine their anti-proliferative and pro-apoptotic action in DU-145 prostate cancer cells. Materials and Methods: Cell death analysis, immunoblotting, RT-PCR analysis, and caspase activity assay were used. Results: EGCG+ibuprofen treatment resulted in 90% growth inhibition, while ibuprofen or EGCG alone reduced cell numbers by 25% and 20%, respectively. EGCG+ibuprofen induced MAPK activation, caspase activation and the inhibition of Bfl-1 expression, all of which were blocked by the antioxidant, N-acetyl-L-cysteine (NAC). Moreover, addition of ceramide rescued the NAC-inhibited MAPK activation and pretreatment with the ceramide synthase inhibitor, fumonisin B1, reduced cell death. Conclusion: Our results suggest that in DU-145 prostate cancer cells: (i) EGCG+ibuprofen treatment has a synergistic effect on apoptosis, and (ii) oxidative stress, directly or indirectly via ceramide synthesis mediates pro-apoptotic signaling. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -