Journal Article

Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells

Nianzeng Xing, Yi Chen, Susan H. Mitchell and Charles Y.F. Young

in Carcinogenesis

Volume 22, issue 3, pages 409-414
Published in print March 2001 | ISSN: 0143-3334
Published online March 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.3.409
Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells

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The androgen receptor (AR) is involved in the development and progression of prostate cancer. In order to find new compounds that may present novel mechanisms to attenuate the function of AR, we investigated the effect of a natural flavonoid chemical, quercetin, on androgen action in an androgen-responsive LNCaP prostate cancer cell line. Western blot analysis showed that AR protein expression was inhibited by quercetin in a dose-dependent manner. To demonstrate that the repression effects on AR expression can actually reduce its function, we found that quercetin inhibited the secretion of the prostate-specific, androgen-regulated tumor markers, PSA and hK2. The mRNA levels of androgen-regulated genes such as PSA, NKX3.1 as well as ornithine decarboxylase (ODC) were down-regulated by quercetin. Transient transfections further showed that quercetin inhibited AR-mediated PSA expression at the transcription level. Finally, it was demonstrated that quercetin could repress the expression of the AR gene at the transcription level. Our result suggests that quercetin can attenuate the function of AR by repressing its expression and has the potential to become a chemopreventive and/or chemotherapeutic agent for prostate cancer.

Keywords: AR, androgen receptor; FCS, fetal calf serum; β-gal, β-galactosidase; hK2, human glandular kallikrein; Mib, mibolerone; ODC, ornithine decarboxylase; PSA, prostate-specific antigen.

Journal Article.  4056 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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