title: Effects of alpha(1)-adrenoceptor (alpha(1)-AR) antagonists on cell proliferation and apoptosis in the prostate: therapeutic implications in prostatic disease.
abstract: BACKGROUND
  Benign prostate hyperplasia (BPH) and prostate cancer established that disruption of the molecular mechanisms that regulate apoptosis and cell proliferation among the stromal and epithelial cell populations, may underlie the neoplastic development that characterizes the aging gland. This work examined the effects of selected alpha(1)-adrenoceptor (alpha(1)-AR) antagonists (blockers) on cellular dynamics to determine whether induction of apoptosis or inhibition of proliferation could contribute to the overall clinical profile.
  
  
  METHODS
  Our efforts were focused on investigating whether alpha(1)-AR antagonists of two different chemical classes affect prostate pathophysiology via mechanisms other than smooth muscle contraction. In in vitro experiments, the two clinically used quinazoline alpha(1)-adrenoceptor antagonists terazosin and doxazosin and the chemically-distinct sulphonamide, tamsulosin, were examined for effects on prostatic tumor growth, by inhibiting cell proliferation and'or inducing apoptosis.
  
  
  RESULTS
  Our findings suggest that alpha(1)-AR antagonists, terazosin and doxazosin, suppress prostatic growth by inducing apoptosis in a dose-dependent manner and without affecting cell proliferation. Tamsulosin exerted no effect on prostate cancer cell growth. The apoptotic effect of terazosin and doxazosin appears to be independent of the alpha(1)-adrenoceptor block.
  
  
  CONCLUSIONS
  Taken together, our findings demonstrate the ability of the quinazoline alpha-blockers, terazosin and doxazosin, but not the sulphonamide, tamsulosin, to suppress prostate growth by inducing apoptosis among the epithelial cells in the benign and malignant prostate. These studies underwrite the durability of the response seen in long-term studies with terazosin, and suggest the potential of this drug in the treatment of prostate carcinoma.
authors.affiliation: Division of Urology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. NKyprianou@smail.umaryland.edu
authors.forename: N
authors.initials: N
authors.lastname: Kyprianou
authors.forename: J
authors.initials: J
authors.lastname: Chon
authors.forename: C M
authors.initials: CM
authors.lastname: Benning
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D002455:Cell Division / Q000187:drug effects*; D017292:Doxazosin / Q000494:pharmacology; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011467:Prostate / Q000473:pathology*; D011469:Prostatic Diseases / Q000188:drug therapy* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; C041226:Terazosin; D000077409:Tamsulosin; D017292:Doxazosin; D011224:Prazosin