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Int. J. Mol. Sci. 2016, 17(8), 1339; doi:10.3390/ijms17081339

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers

1
School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia
2
Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4226, Australia
3
Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 6 July 2016 / Revised: 5 August 2016 / Accepted: 8 August 2016 / Published: 16 August 2016
(This article belongs to the Collection Advances in Molecular Oncology)
View Full-Text   |   Download PDF [1842 KB, uploaded 16 August 2016]   |  

Abstract

This review evaluates the role of α-adrenoceptor antagonists as a potential treatment of prostate cancer (PCa). Cochrane, Google Scholar and Pubmed were accessed to retrieve sixty-two articles for analysis. In vitro studies demonstrate that doxazosin, prazosin and terazosin (quinazoline α-antagonists) induce apoptosis, decrease cell growth, and proliferation in PC-3, LNCaP and DU-145 cell lines. Similarly, the piperazine based naftopidil induced cell cycle arrest and death in LNCaP-E9 cell lines. In contrast, sulphonamide based tamsulosin did not exhibit these effects. In vivo data was consistent with in vitro findings as the quinazoline based α-antagonists prevented angiogenesis and decreased tumour mass in mice models of PCa. Mechanistically the cytotoxic and antitumor effects of the α-antagonists appear largely independent of α 1-blockade. The proposed targets include: VEGF, EGFR, HER2/Neu, caspase 8/3, topoisomerase 1 and other mitochondrial apoptotic inducing factors. These cytotoxic effects could not be evaluated in human studies as prospective trial data is lacking. However, retrospective studies show a decreased incidence of PCa in males exposed to α-antagonists. As human data evaluating the use of α-antagonists as treatments are lacking; well designed, prospective clinical trials are needed to conclusively demonstrate the anticancer properties of quinazoline based α-antagonists in PCa and other cancers. View Full-Text
Keywords: α1-adrenoceptor antagonist; prostate cancer; cytotoxicity α1-adrenoceptor antagonist; prostate cancer; cytotoxicity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Batty, M.; Pugh, R.; Rathinam, I.; Simmonds, J.; Walker, E.; Forbes, A.; Anoopkumar-Dukie, S.; McDermott, C.M.; Spencer, B.; Christie, D.; Chess-Williams, R. The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers. Int. J. Mol. Sci. 2016, 17, 1339.

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