α1-Adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia

Joanna K. Chon, Andrew Borkowski, Alan W. Partin, John T. Isaacs, Stephen C. Jacobs, Natasha Kyprianou

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Recent evidence indicated that an α1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by α1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another α1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. Materials and Methods: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle α-actin immunoreactivity. Results: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p <0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both α1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle α- actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. Conclusions: These findings demonstrate that α-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to α1 blockade in the treatment of BPH.

Original languageEnglish (US)
Pages (from-to)2002-2008
Number of pages7
JournalJournal of Urology
Volume161
Issue number6
DOIs
StatePublished - Jun 1999
Externally publishedYes

Keywords

  • Apoptosis
  • Cell proliferation
  • Doxazosin
  • Prostate
  • Terazosin
  • α-adrenoceptor antagonists

ASJC Scopus subject areas

  • Urology

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