title: The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers.
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.
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. mallory.batty@griffithuni.edu.au.
authors.forename: Mallory
authors.initials: M
authors.lastname: Batty
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. rachel.pugh@griffithuni.edu.au.
authors.forename: Rachel
authors.initials: R
authors.lastname: Pugh
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. ilampirai.rathinam@griffithuni.edu.au.
authors.forename: Ilampirai
authors.initials: I
authors.lastname: Rathinam
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. joshua.simmonds@griffithuni.edu.au.
authors.forename: Joshua
authors.initials: J
authors.lastname: Simmonds
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. edwin.walker@griffithuni.edu.au.
authors.forename: Edwin
authors.initials: E
authors.lastname: Walker
authors.affiliation: Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4226, Australia. amanda.forbes@student.bond.edu.au.
authors.forename: Amanda
authors.initials: A
authors.lastname: Forbes
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. s.dukie@griffith.edu.au.|Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia. s.dukie@griffith.edu.au.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Anoopkumar-Dukie
authors.affiliation: Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4226, Australia. camcderm@bond.edu.au.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: McDermott
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. b.spencer@griffith.edu.au.
authors.forename: Briohny
authors.initials: B
authors.lastname: Spencer
authors.affiliation: School of Pharmacy, Griffith University, Gold Coast, QLD 4222, Australia. David.Christie@genesiscare.com.au.|Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4226, Australia. David.Christie@genesiscare.com.au.
authors.forename: David
authors.initials: D
authors.lastname: Christie
authors.affiliation: Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4226, Australia. rchesswi@bond.edu.au.
authors.forename: Russ
authors.initials: R
authors.lastname: Chess-Williams
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017292:Doxazosin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000970:Antineoplastic Agents; C041226:Terazosin; D017292:Doxazosin; D011224:Prazosin
keywords: cytotoxicity; prostate cancer; α1-adrenoceptor antagonist