Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells

Recently, studies have investigated the significance of the Wnt/beta-catenin pathway in prostate cancer. The transcriptional activity of the androgen receptor (AR) is modulated by interaction with coregulators, one of which is beta-catenin. Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a chemopreventive role. Although curcumin has been shown to inhibit AR expression, its molecular mechanism has not been fully elucidated. In this study, whether curcumin mediates the Wnt/beta-catenin signaling pathway with regard to AR/beta-catenin interactions was studied. Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of beta-catenin was shown in the nuclear and cytoplasmic extracts as well as whole cell lysates. Further analysis revealed that phosphorylation of Akt and glycogen synthase kinase-3 beta were attenuated, but phosphorylated beta-catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the target gene of the beta-catenin/T-cell factor transcriptional complex, were also decreased. These findings suggest that curcumin modulates the Wnt/beta-catenin signaling pathway and might have a significant role in mediating inhibitory effects on LNCaP prostate cancer cells. Prostate Cancer and Prostatic Diseases (2010) 13, 343-349; doi: 10.1038/pcan.2010.26; published online 3 August 2010