The role of alpha 1-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
Pages (from-to)1-26
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume17
Issue number8
DOIs
Publication statusPublished - 16 Aug 2016

Fingerprint

Quinazolines
Adrenergic Receptors
Prostatic Neoplasms
Terazosin
tamsulosin
cancer
Cells
Doxazosin
cultured cells
Caspase 8
Prazosin
Sulfonamides
Cell proliferation
Cell growth
Cell death
Cell Line
Vascular Endothelial Growth Factor A
Tumors
angiogenesis
Cell Cycle Checkpoints

Cite this

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. / The role of alpha 1-adrenoceptor antagonists in the treatment of prostate and other cancers. In: International Journal of Molecular Sciences. 2016 ; Vol. 17, No. 8. pp. 1-26.
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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.",
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Batty, M, Pugh, R, Rathinam, I, Simmonds, J, Walker, E, Forbes, A, Anoopkumar-Dukie, S, McDermott, CM, Spencer, B, Christie, D & Chess-Williams, R 2016, 'The role of alpha 1-adrenoceptor antagonists in the treatment of prostate and other cancers' International Journal of Molecular Sciences, vol. 17, no. 8, pp. 1-26. https://doi.org/10.3390/ijms17081339

The role of alpha 1-adrenoceptor antagonists in the treatment of prostate and other cancers. / 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.

In: International Journal of Molecular Sciences, Vol. 17, No. 8, 16.08.2016, p. 1-26.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The role of alpha 1-adrenoceptor antagonists in the treatment of prostate and other cancers

AU - Batty, Mallory

AU - Pugh, Rachel

AU - Rathinam, Ilampirai

AU - Simmonds, Joshua

AU - Walker, Edwin

AU - Forbes, Amanda

AU - Anoopkumar-Dukie, Shailendra

AU - McDermott, Catherine M

AU - Spencer, Briohny

AU - Christie, David

AU - Chess-Williams, Russ

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N2 - 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.

AB - 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.

U2 - 10.3390/ijms17081339

DO - 10.3390/ijms17081339

M3 - Article

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EP - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

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ER -