The cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c-Jun in prostate cancer cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in cancer chemoprevention. In this study, we investigated the effects of NSAIDs on androgen receptor (AR)-mediated functions in prostate cancer cells. We found that two cyclooxygenase 2-specific NSAIDs, celecoxib and nimesulide, dramatically reduced the expression of androgen-inducible genes, such as prostate-specific antigen, hK2, and the FK506-binding protein 51 (FKBP51). We demonstrated that both NSAIDs repressed AR-mediated activation of prostate-specific antigen and hK2 promoter activity as well as AR protein expression. Finally, our findings suggested that overexpressed c-Jun by the NSAIDs not only inhibited the function of AR but also directly repressed AR expression at the transcription level. Our findings provide a strong rationale for celecoxib and nimesulide as potential agents for prostate cancer prevention and/or treatment.
Pan
Yunqian
Y
Departments of Urology and Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic/Foundation, Rochester, Minnesota 55905.
Zhang
Jin-San
JS
Gazi
Mozammel H
MH
Young
Charles Y F
CY
D059002:Androgen Receptor Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D000068579:Celecoxib; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099159:Tacrolimus Binding Protein 5
D059002:Androgen Receptor Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000068579:Celecoxib; D011720:Pyrazoles; D013449:Sulfonamides; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C012655:nimesulide