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

Prostate Cancer Prostatic Dis. 2010 Dec;13(4):343-9. doi: 10.1038/pcan.2010.26. Epub 2010 Aug 3.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Binding / drug effects
  • Receptors, Androgen / metabolism*
  • Signal Transduction / drug effects
  • Wnt1 Protein / metabolism*
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • Receptors, Androgen
  • Wnt1 Protein
  • beta Catenin
  • Curcumin