Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth.

@article{citeulike:1100343, abstract = {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.}, address = {Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.}, author = {Cha, T. L. and Qiu, L. and Chen, C. T. and Wen, Y. and Hung, M. C. }, citeulike-article-id = {1100343}, doi = {http://dx.doi.org/10.1158/0008-5472.CAN-04-3250}, issn = {0008-5472}, journal = {Cancer Res}, keywords = {resveratrol}, month = {March}, number = {6}, pages = {2287--2295}, posted-at = {2007-02-11 10:28:29}, priority = {2}, title = {Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth.}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-04-3250}, volume = {65}, year = {2005} }

TY - JOUR ID - citeulike:1100343 L3 - citeulike-article-id:1100343 TI - Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. JF - Cancer Res VL - 65 IS - 6 SP - 2287 EP - 2295 AD - Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. SN - 0008-5472 N2 - 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. KW - resveratrol AU - Cha, TL AU - Qiu, L AU - Chen, CT AU - Wen, Y AU - Hung, MC PY - 2005/03/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-04-3250 ER -