Research Papers:

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction

Defeng Xu _, Qiulu Chen, Yalin Liu and Xingqiao Wen

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Oncotarget. 2017; 8:105561-105573. https://doi.org/10.18632/oncotarget.22319

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Defeng Xu1, Qiulu Chen1, Yalin Liu1 and Xingqiao Wen2

1School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China

2Department of Urology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong 518100, P.R. China

Correspondence to:

Defeng Xu, email: [email protected]

Xingqiao Wen, email: [email protected]

Keywords: anti-androgen; baicalein; flavonoids; prostate cancer; androgen receptor

Received: March 28, 2017     Accepted: June 28, 2017     Published: November 06, 2017


Background: Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression.

Methods: PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression.

Results: The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction.

Conclusions: Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

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