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Published on: November 15, 2013
Inhibition of the androgen receptor activity by Coprinus comatus substances
Nesly Dotan1, Solomon P Wasser, Jamal Mahajna
1MIGAL-Galilee Technology Center, Cancer Drug Discovery Program, Kiryat Shmona, Israel.
Abstract:
Prostatic adenocarcinoma is the second leading cause of death from cancer in Western men. The common prostate cancer treatments are effective in the early stages; however, advanced prostate cancer is resilient to most of these treatments. Altered androgen receptor (AR) activity caused by point mutations or signaling mechanisms that regulate AR function has been proposed as a key mechanism in the transition to the androgen-independent stage. Our previous results demonstrated that hexane extract prepared from Coprinus comatus (C. comatus) strain 734 was able to interfere with AR activity. The current study was made to further evaluate the antiandrogenic activity of the C. comatus mushroom strain 734. Activity-guided chromatography was conducted and 2 active fractions, F-32-and F-33, were found to contain substances that were able to inhibit AR-mediated reporter activity and reduce the levels of AR and prostate-specific antigen (PSA) transcripts in LNCaP cells. Fraction F-32 also inhibited the proliferation and clonigenicity of LNCaP cells. Furthermore, F-32 was able to inhibit the binding of AR to the PSA enhancer region and to inhibit Akt-mediated AR phosphorylation at Ser 213. This study illustrated the potential of substances from the C. comatus mushroom to serve as natural antiandrogenic modulators for the treatment of prostatic disorders.
Insights
Coprinus comatus mushroom extract shows potential as a natural treatment for advanced prostate cancer. It effectively inhibits androgen receptor (AR) activity, reducing cancer cell growth and proliferation.
Area of Science:
- Mycology
- Oncology
- Molecular Biology
Background:
- Prostate cancer, particularly advanced stages, is a significant cause of cancer death in Western men.
- Current treatments for advanced prostate cancer are often ineffective due to resistance.
- Altered androgen receptor (AR) activity is a key factor in the progression to androgen-independent prostate cancer.
Purpose of the Study:
- To evaluate the antiandrogenic activity of the mushroom Coprinus comatus (C. comatus) strain 734.
- To identify active compounds from C. comatus that can modulate androgen receptor (AR) signaling.
- To explore the therapeutic potential of C. comatus in treating prostate disorders.
Main Methods:
- Activity-guided chromatography was used to isolate active fractions from C. comatus extract.
- Inhibition of AR-mediated reporter activity and AR/PSA transcript levels in LNCaP cells was assessed.
- Cell proliferation, clonigenicity, AR-DNA binding, and Akt-mediated AR phosphorylation were evaluated.
Main Results:
- Two active fractions, F-32 and F-33, inhibited AR-mediated reporter activity and reduced AR and prostate-specific antigen (PSA) transcript levels.
- Fraction F-32 inhibited LNCaP cell proliferation and clonigenicity.
- F-32 also inhibited AR binding to the PSA enhancer region and Akt-mediated AR phosphorylation.
Conclusions:
- Substances from C. comatus mushroom strain 734 possess significant antiandrogenic activity.
- C. comatus derived compounds can inhibit key mechanisms driving prostate cancer progression.
- C. comatus shows potential as a source of natural antiandrogenic modulators for treating prostatic disorders.
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