作者: Naghma Khan , Mohammad Asim , Farrukh Afaq , Mohammad Abu Zaid , Hasan Mukhtar
DOI: 10.1158/0008-5472.CAN-08-0240
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摘要: Androgen receptor (AR)-mediated signaling plays an important role in the development and progression of prostate cancer (PCa). Hormonal therapies, mainly with combinations antiandrogens androgen deprivation, are mainstay treatment for advanced disease. However, emergence resistance largely due to inefficient antihormone action limits their therapeutic usefulness. Here, we report that fisetin, a novel dietary flavonoid, acts as AR ligand by competing high-affinity interact binding domain AR. We show this physical interaction results substantial decrease stability amino-terminal/carboxyl-terminal (N-C) This blunting AR-mediated transactivation target genes including prostate-specific antigen (PSA). In addition, LNCaP cells fisetin decreased protein levels, part, decreasing its promoter activity accelerating degradation. Fisetin also synergized Casodex inducing apoptosis cells. Treatment athymic nude mice implanted AR-positive CWR22Rupsilon1 human PCa resulted inhibition tumor growth reduction serum PSA levels. These data identify inhibitor axis suggest it could be useful chemopreventive chemotherapeutic agent delay PCa.