RT Journal Article SR Electronic T1 Synergistic Cell Death by EGCG and Ibuprofen in DU-145 Prostate Cancer Cell Line JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3947 OP 3956 VO 27 IS 6B A1 KIM, MYOUNG H. A1 CHUNG, JAEGWON YR 2007 UL http://ar.iiarjournals.org/content/27/6B/3947.abstract AB 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