Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component

Prostate Cancer Prostatic Dis. 2002;5(2):88-95. doi: 10.1038/sj.pcan.4500561.

Abstract

alpha(1)-Adrenoceptor antagonists, have been documented to induce apoptosis and reduce prostate tumor vascularity in benign and malignant prostate cells. The quinazoline based alpha(1)-antagonists, doxazosin and terazosin but not tamsulosin (a sulphonamide derivative) suppress prostate growth without affecting cell proliferation. These quinazoline-mediated apoptotic effects occur via an alpha(1)-adrenoceptor independent mechanism potentially involving activation of the TGF-beta signal transduction pathway. This review discusses the current knowledge of the action of quinazoline-derived alpha(1)-adrenoceptor antagonists in the benign and malignant prostate and their potential therapeutic use in the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Finally, a molecular pathway is proposed for their observed apoptotic function against prostate cells. Increased understanding of the action of these established and clinically accepted agents would provide a basis for the design of safe, effective therapeutic regimens in the treatment of prostatic diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Antagonists / pharmacology*
  • Apoptosis*
  • Humans
  • Male
  • Prostatic Hyperplasia / physiopathology*
  • Prostatic Neoplasms / physiopathology*
  • Quinazolines / pharmacology*
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Adrenergic Antagonists
  • Quinazolines
  • Receptors, Adrenergic, alpha-1