題名: Emodin downregulates androgen receptor and inhibits prostate cancer cell growth
作者: Cha, T-L.;Qiu, L.;Chun-Te Chen;Wem, Y;Mien-Chie Hung
關鍵詞: emodin;androgen receptor;proteasome degradation;prostate cancer 日期: 2005-03
上傳時間: 2009-11-27T05:57:04Z 出版者: Asia University
摘要: Hormone-refractory relapse is an inevitable and lethal event for
advanced prostate cancer patients after hormone deprivation. A growing body of evidence indicates that hormone deprivation may promote this aggressive prostate cancer phenotype. Notably, androgen receptor (AR) not only mediates the effect of androgen on the tumor initiation but also plays the major role in the relapse transition. This provides a strong rationale for searching new effective agents targeting the down- regulation of AR to treat or prevent advanced prostate cancer progression. Here, we show that emodin, a natural compound, can directly target AR to suppress prostate cancer cell growth in vitro and prolong the survival of C3(1)/SV40 transgenic mice in vivo. Emodin treatment resulted in repressing androgen-dependent transactivation of AR by inhibiting AR nuclear translocation. Emodin decreased the
association of AR and heat shock protein 90 and increased the association of AR and MDM2, which in turn induces AR degradation through proteasome-mediated pathway in a ligand-independent manner.
Our work indicates a new mechanism for the emodin-mediated anticancer effect and justifies further investigation of emodin as a therapeutic and preventive agent for prostate cancer.
