Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway

Abstract

Activation of the Wingless (Wnt)/β-catenin signaling pathway contributes to prostate tumorigenesis and metastasis. Depending of the stage of prostate cancer development, current drug therapies are of limited efficiency, so that prevention with natural compounds appears as an attractive strategy especially due to the slow progressive development of prostate cancer. We report here that the chemopreventive agent curcumin from the rhizome of Curcuma longa was able to affect cell proliferation of androgen-dependent prostate cancer through the induction of cell cycle arrest in G2 and modulation of Wnt signaling. Curcumin decreases the level of Tcf-4, CBP and p300 proteins implicated in the Wnt transcriptional complex that leads to the decrease of β-catenin/Tcf-4 transcriptional activity and of the expression of β-catenin target genes (cyclin D1 and c-myc). Subsequent cell death induction is linked to autophagy. Interestingly, in androgen-independent prostate cancer cells, curcumin does not affect Wnt/β-catenin transcriptional activity. Altogether our results suggest that curcumin is an interesting chemopreventive agent for early stage prostate cancer.