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/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.
Choi
H Y
HY
Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lim
J E
JE
Hong
J H
JH
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051155:Wnt1 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D051155:Wnt1 Protein; D051176:beta Catenin; D003474:Curcumin