Abstract 3804: Transcriptional repression of androgen receptor in human prostate cancer cells by plant flavone apigenin

Accumulating evidence suggest that androgen receptor (AR)-mediated signaling plays an important role in the development and progression of prostate cancer. Although Prostate Cancer Prevention Trial (PCPT) showed controversial results however manipulation of AR signaling pathway reduced the incidence of prostate cancer. Safer agents are needed that can modulate AR signaling pathways with effective suppression of prostate cancer. Plant flavonoids have been shown to possess weak oestrogenic and anti-androgen activity. Apigenin, a naturally occurring plant flavone, has shown promising anticancer activity by modulating several signaling pathways that have relevance to prostate cancer. However, the effect of apigenin on AR signaling has not been fully investigated. Using androgen-responsive human prostate cancer LNCaP and 22Rv1cells, we determine the effect of apigenin on androgen receptor signaling. Exposure of these cells with 5-40μM apigenin suppressed cell proliferation and arrested cells in sub G0-G1 phase of the cell cycle after 5nM dihydrotestosterone (DHT) stimulation. Apigenin inhibited endogenous prostate-specific antigen (PSA) transcription and reduced intracellular and secreted PSA protein levels induced by DHT in these cells. In LNCaP cells apigenin inhibited AR expression in a concentration-dependent manner by restricting its translocation into the nucleus. Co-transfection of PC-3 cells with wild-type AR-GFP-tag plasmid demonstrated that apigenin has ability to inhibit DHT-induced AR translocation into the nucleus. Additionally, receptor binding assays indicated that apigenin is a strong competitive inhibitor of DHT binding to the AR. These observations matched with the results of structural modeling studies exhibiting that apigenin is remarkably similar in conformational geometry and surface charge distribution to synthetic AR antagonist, flutamide, although the atomic compositions of the two substances were quite different. Taken together, our results indicate that apigenin exhibits potent anti-proliferative and anti-androgenic properties and may be developed as useful and safer agent for prevention/therapy of prostate cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3804.