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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function
Shashwati Basak1, Deepa Pookot, Emily J Noonan
1Department of Urology, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Molecular Cancer Therapeutics
|October 15, 2008
Summary
Genistein, a soy isoflavone, reduces prostate cancer
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Androgen receptor (AR) is crucial for prostate cancer development.
- Genistein (soy isoflavone) previously showed AR down-regulation in prostate cancer cells.
- The exact mechanism of genistein-induced AR down-regulation remained unclear.
Purpose of the Study:
- To elucidate the novel mechanism by which genistein down-regulates AR protein levels.
- To investigate the role of Hsp90 chaperone activity and HDAC6 in genistein's effect.
Main Methods:
- Assessed AR ubiquitination in genistein-treated LNCaP cells.
- Evaluated Hsp90 chaperone activity and acetylation status.
- Investigated the effect of genistein on HDAC6 activity.
Main Results:
- Genistein treatment increased AR ubiquitination, indicating proteasomal degradation.
- Genistein decreased Hsp90 chaperone activity by promoting its acetylation.
- Genistein inhibited HDAC6, a Hsp90 deacetylase, reducing its cochaperone function.
Conclusions:
- Genistein down-regulates AR by inhibiting the HDAC6-Hsp90 complex, disrupting AR stabilization.
- Genistein represents a potential chemopreventive agent for prostate cancer.
- Combination therapy with genistein and HDAC6/Hsp90 inhibitors may be beneficial.
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