Mechanism of curcumin prostate cancer suppression revealed
MedWire News: Curcumin may play a role in inhibiting androgen expression in prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway, the results of a preliminary study indicate.
Lifestyle factors, such as diet, are known to affect prostate cancer risk. For example, people in southeast Asia have a low incidence of prostate cancer and a high consumption of curcumin, which is a chemoprotectant against prostate cancer and inhibits the expression of androgen receptor (AR) and AR-related factors.
To examine the mechanisms by which curcumin regulates AR expression in prostate cancer, J Hong, from Dankook University College of Medicine in Cheonan, Republic of Korea, and colleagues performed a series of experiments to assess whether curcumin mediates the Wnt/beta-catenin signaling pathway through AR/beta-catenin interactions in androgen-dependent LNCaP prostate cancer cells.
Curcumin inhibited proliferation of LNCaP in a dose-dependent manner, and a similar effect was seen on AR expression, with AR expression reduced by 52% and 84% at doses of 20 µM and 25 µM, respectively.
In addition, beta-catenin was suppressed by curcumin treatment particularly in nuclear cell extracts, as well as in cytoplasmic cell extracts and whole-cell lysates. The team found that curcumin reduced the phosphorylation of Akt and glycogen synthase kinase-3beta, while phosphorylation of beta-curcumin was increased.
The findings, published in the journal Prostate Cancer and Prostatic Disease, also revealed that expression of cyclin D1 and c-myc, which is the target gene of the beta-catenin/T-cell factor transcriptional complex, was reduced.
The researchers write: "The results here are presented that the curcumin induced the degradation of beta-catenin through regulation of downstream intermediates in the Wnt/beta-catenin pathway.
"Given the fact that beta-catenin acts as a transcriptional coactivator of AR, these results provide evidence whereby curcumin can affect LNCaP cell proliferation and growth through modulation of both Wnt/beta-catenin and androgen signaling."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Liam Davenport