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Published on: May 16, 2012
Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth
Tai-Lung Cha1, Lin Qiu, Chun-Te Chen
1Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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.
Insights
Emodin, a natural compound, effectively suppresses prostate cancer cell growth by targeting the androgen receptor (AR). This compound offers a promising therapeutic strategy for advanced prostate cancer, inhibiting AR activity and promoting its degradation.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hormone-refractory relapse is a critical challenge in advanced prostate cancer.
- Androgen receptor (AR) signaling is central to prostate cancer initiation and progression.
- Targeting AR down-regulation is a key strategy for novel prostate cancer therapies.
Purpose of the Study:
- To investigate the potential of emodin, a natural compound, as a therapeutic agent for prostate cancer.
- To elucidate the mechanism by which emodin affects androgen receptor (AR) activity and prostate cancer cell growth.
Main Methods:
- In vitro studies on prostate cancer cell lines.
- In vivo studies using C3(1)/SV40 transgenic mice.
- Analysis of AR nuclear translocation, AR-HSP90, and AR-MDM2 interactions.
- Assessment of proteasome-mediated AR degradation.
Main Results:
- Emodin directly targets the androgen receptor (AR), suppressing prostate cancer cell growth in vitro.
- Emodin treatment prolonged survival in a mouse model of prostate cancer.
- Emodin inhibited AR nuclear translocation and androgen-dependent transactivation.
- Emodin promoted AR degradation via the proteasome pathway by altering AR-HSP90 and AR-MDM2 associations.
Conclusions:
- Emodin demonstrates anticancer effects by directly targeting and degrading the androgen receptor (AR) in a ligand-independent manner.
- The findings reveal a novel mechanism for emodin's anticancer activity.
- Emodin warrants further investigation as a potential therapeutic and preventive agent for prostate cancer.
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