Kaempferol (Kae) is one of the most important constituents in ginkgo biloba extract which has been well known for its antioxidant and anti-inflammatory activities. Kae is also reported to suppress the growth of cancer cells but the mechanism of cell death induction is not fully understood. In the present study, we performed in vitro studies, for the first time to examine whether Kae induces apoptotic cell death in human prostate cancer cells and if β-Catenin signaling pathway is involved in the Kae-induced apoptosis. Kae treatment was found to decrease viability of human prostate cancer PC-3 (androgen independent, p53 null) and LNCaP (androgen responsive, wild-type p53) cells at pharmacologically achievable concentrations (10-40 µmol/L at 24 h). The anti-cancer activity by Kae was caused by apoptosis induction, which was determined by increased cytoplasmic histone-associated DNA fragmentation, caspase 3 activities and sub-G0/G1 cell phase in PC-3 and LNCaP cells treated with Kae compared with controls. Interestingly, a normal human prostate epithelial cell line (PrEC) is significantly more resistant to growth inhibition and apoptosis induction by Kae. Exposure of PC-3 and LNCaP cells to Kae resulted in significant inhibition of β-Catenin protein levels by Elisa assay, down-regulation of protein expression of β-Catenin as well as its down stream targets C-myc, Cyclin D1 and survivin, and alteration in nuclear/cytoplasmic distribution of β-Catenin by immunoblotting. Moreover, Kae treatment significantly inhibited the β-Catenin/TCF transcriptional activity in PC-3 and LNCaP cells transiently transfected with the TCF-4 reporter assay. We also found that apoptosis induction by Kae in human prostate cancer cells correlates with suppression of androgen receptor (AR), phosphor-AR and PSA protein levels. In conclusion, the present study indicates that β-Catenin as well as AR signaling pathways may be targets for Kae-induced apoptosis in human prostate cancer cells. This investigation was supported by USPHS grant R21 CA143104-02, awarded by the National Cancer Institute.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2011-5568

©2011 American Association for Cancer Research
2011