The role of α1-adrenoceptor antagonists in the treatment of prostate and other cancers

Mallory Batty, Rachel Pugh, Ilampirai Rathinam, Joshua Simmonds, Edwin Walker, Amanda Forbes, Shailendra Anoopkumar-Dukie, Catherine M McDermott, Briohny Spencer, David Christie, Russ Chess-Williams

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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 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.

Original languageEnglish
Article number1339
Pages (from-to)1-26
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume17
Issue number8
DOIs
Publication statusPublished - 16 Aug 2016

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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. (2016). The role of α1-adrenoceptor antagonists in the treatment of prostate and other cancers. International Journal of Molecular Sciences, 17(8), 1-26. [1339]. https://doi.org/10.3390/ijms17081339