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Stilbenes Inhibit Androgen Receptor Expression in 22Rv1 Castrate-resistant Prostate Cancer Cells

Author:
Kumar, Avinash, Lin, Shih-Yun, Dhar, Swati, Rimando, Agnes M., Levenson, Anait S.
Source:
Journal of medicinally active plants 2014 v.3 no.1-4 pp. 1
ISSN:
2159-7200
Subject:
agonists, androgen receptors, cell growth, cell proliferation, chemoprevention, dose response, growth retardation, neoplasm cells, prostatic neoplasms, pterostilbene, resveratrol, therapeutics, transcriptional activation
Abstract:
Androgen receptor (AR) signaling plays an important role in the development and progression of prostate cancer (PCa). Importantly, AR continues to be expressed in advanced stages of castrate-resistant PCa (CRPC), where it can have ligand- independent activity. Identification of naturally occurring substances which can inhibit AR expression holds promise for PCa chemoprevention and therapy. We have previously shown that resveratrol (Res) inhibits androgen-promoted growth, AR expression and transactivation in androgen-responsive non-metastatic LNCaP PCa cells. In the current study, we investigated the effects of Res and its three natural analogs: trimethoxy-resveratrol (3M-Res), pterostilbene (Pter) and piceatannol (Pic) on growth of 22Rv1 castrate-resistant cells, which express wild type (AR114/110) and truncated form (AR80) of AR. We found that although all the stilbenes inhibited the proliferation of 22Rv1 cells in a dose-dependent manner, 3M-Res was the most potent inhibitor. We also found that while AR114/110 responded to the synthetic androgen agonist methyltrienolone (R1881) as well as to antiandrogen Flutamide AR80, which lacks ligand-binding domain, did not respond to R1881 but was inhibited by Flutamide. Interestingly, Res, Pter and Pic but not 3M-Res, like Flutamide, inhibited both AR114/110 and AR80, with the effect on AR80 being more prominent when high concentrations of the stilbenes were used. Taken together, these data indicate both AR-independent (3M-Res) and possible AR-dependent (Res, Pter, Pic) mechanisms of cell growth inhibition by these stilbenes. These findings provide evidence for the potential use of these stilbenes in arresting the progression of CRPC.
Agid:
62341
Handle:
10113/62341