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Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells

Department of Anatomy, Chonnam National University Medical School, Gwangju 61469, Korea
Department of Statistics, College of Natural Sciences, Chonnam National University, Gwangju 61186, Korea
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(10), 3062;
Received: 8 August 2018 / Revised: 21 September 2018 / Accepted: 1 October 2018 / Published: 8 October 2018
(This article belongs to the Special Issue The Effect of Dietary Factors on Cancer)
The prostate gland contains a high level of intracellular zinc, which is dramatically diminished during prostate cancer (PCa) development. Owing to the unclear role of zinc in this process, therapeutic applications using zinc are limited. This study aimed to clarify the role of zinc and its underlying mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly inhibited the androgen-mediated transactivation and expression of the androgen target, prostate specific antigen (PSA). This phenomenon resulted from facilitated protein degradation, not transcriptional control. In studies using mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc significantly reduced tumor size. Analyses of both xenograft tumors and normal prostates showed reduced expression of AR and increased cell death. Considering the significant loss of intracellular zinc and the dominant growth-modulating role of AR during PCa development, loss of zinc may be a critical step in the transformation of normal cells to cancer cells. This study provides the underlying mechanism by which zinc functions as a PCa suppressor, and forms the foundation for developing zinc-mediated therapeutics for PCa. View Full-Text
Keywords: zinc; prostate cancer; androgen receptor zinc; prostate cancer; androgen receptor
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MDPI and ACS Style

To, P.K.; Do, M.-H.; Cho, Y.-S.; Kwon, S.-Y.; Kim, M.S.; Jung, C. Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells. Int. J. Mol. Sci. 2018, 19, 3062.

AMA Style

To PK, Do M-H, Cho Y-S, Kwon S-Y, Kim MS, Jung C. Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells. International Journal of Molecular Sciences. 2018; 19(10):3062.

Chicago/Turabian Style

To, Phuong Kim, Manh-Hung Do, Young-Suk Cho, Se-Young Kwon, Min Soo Kim, and Chaeyong Jung. 2018. "Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells" International Journal of Molecular Sciences 19, no. 10: 3062.

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