A nonsteroidal anti-inflammatory drug, flufenamic acid, inhibits the expression of the androgen receptor in LNCaP cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in chemoprevention of colon cancer and others by inhibiting prostaglandin synthesis. In this report, we used LNCaP cells, an androgen-responsive human prostate carcinoma cell line, to study the effects of two NSAIDs, flufenamic acid (FA) and piroxicam (PXM), on the cancer cell growth stimulated by androgens. We found that FA had much higher potency to inhibit LNCaP cell growth than PXM. FA dramatically reduced the expression of androgen inducible genes, such as prostate-specific antigen (PSA) and the homeo-domain transcription factor Nkx3.1, but PXM did not. In vitro transfection experiments showed that FA down regulated the PSA expression at the transcription level. Western and northern blot analyses demonstrated that FA inhibited the androgen receptor (AR) expression at mRNA and protein levels. Suppressed AR expression may be the cause of FA-mediated inhibition of the androgen inducible gene expression. Our data also showed that FA significantly reduced the AR promoter-mediated transcription activities. This study indicated that AR might be a target for FA to inhibit LNCaP cell growth. FA and other similar NSAIDs may be potential candidates for chemoprevention of human prostate cancer by modulating the expression of AR.
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Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Smith
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Young
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005439:Flufenamic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D010894:Piroxicam / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D011944:Receptors, Androgen; D014157:Transcription Factors; D010894:Piroxicam; D005439:Flufenamic Acid; D017430:Prostate-Specific Antigen