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The Cyclooxygenase 2-specific Nonsteroidal Anti-inflammatory Drugs Celecoxib and Nimesulide Inhibit Androgen Receptor Activity via Induction of c-Jun in Prostate Cancer Cells¹

Departments of Urology and Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic/Foundation, Rochester, Minnesota 55905

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.

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