Synergistic cell death by EGCG and ibuprofen in DU-145 prostate cancer cell line.
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.


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.


CONCLUSIONS
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.
Kim
Myoung H
MH
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA. mkim@hsc.unt.edu
Chung
Jaegwon
J
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D002518:Ceramides / Q000096:biosynthesis / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D008297:Male; D015778:Minor Histocompatibility Antigens; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C096816:BCL2-related protein A1; D002518:Ceramides; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002392:Catechin; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D007052:Ibuprofen