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

Abstract

Recently, studies have investigated the significance of the Wnt/b-catenin pathway in prostate cancer. The transcriptional activity of the androgen receptor (AR) is modulated by interaction with coregulators, one of which is b-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/b-catenin signaling pathway with regard to AR/b-catenin interactions was studied. Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of b-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-3b were attenuated, but phosphorylated b-catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the target gene of the b-catenin/T-cell factor transcriptional complex, were also decreased. These findings suggest that curcumin modulates the Wnt/b-catenin signaling pathway and might have a significant role in mediating inhibitory effects on LNCaP prostate cancer cells.

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“…It exerts likewise proapoptotic activity mainly by decreasing the expression of the anti-apoptotic proteins and by activating proapoptotic enzymes. Curcumin decreases angiogenesis through the inhibition of the vascular endothelial growth factor expression [9] and the inhibition of androgen receptor expression in a dose-dependent manner [10]. …”

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“…Furthermore, we found that CDF, a synthetic analogue of curcumin, could inhibit AR expression and interrupt the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network, leading to the inactivation of Wnt signaling and the inhibition of PCa cell invasion [56]. Similar results were also reported showing that curcumin could interrupt the interaction between AR and Wnt/β-catenin signaling pathways in PCa cells [99]. All these reports suggest the potent inhibitory effects of curcumin or its synthetic analogue on PCa.…”

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“…The main event of the activation of Wnt/β-catenin pathway is the nuclear translocation of beta-catenin, which binds to T-cell factor (TCF) in the nucleus [56]. The intracellular levels of beta-catenin are regulated by the phosphorylation of GSK-3β.…”