The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers
AbstractThis 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
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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.
Batty M, Pugh R, Rathinam I, Simmonds J, Walker E, Forbes A, Anoopkumar-Dukie S, McDermott CM, Spencer B, Christie D, Chess-Williams R. The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers. International Journal of Molecular Sciences. 2016; 17(8):1339.Chicago/Turabian Style
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. 2016. "The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers." Int. J. Mol. Sci. 17, no. 8: 1339.
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