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

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    Author(s)
    Batty, Mallory
    Pugh, Rachel
    Rathinam, Ilampirai
    Simmonds, Joshua
    Walker, Edwin
    Forbes, Amanda
    Anoopkumar-Dukie, Shailendra
    McDermott, Catherine M
    Spencer, Briohny
    Christie, David
    Chess-Williams, Russ
    Griffith University Author(s)
    Spencer, Briohny H.
    Anoopkumar-Dukie, Shailendra
    Year published
    2016
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    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 ...
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    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.
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    Journal Title
    International Journal of Molecular Sciences
    Volume
    17
    Issue
    8
    DOI
    https://doi.org/10.3390/ijms17081339
    Copyright Statement
    © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
    Subject
    Other chemical sciences
    Other chemical sciences not elsewhere classified
    Genetics
    Other biological sciences
    Publication URI
    http://hdl.handle.net/10072/142859
    Collection
    • Journal articles

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