Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component.
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.
Anglin
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Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Glassman
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DT
Kyprianou
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D018674:Adrenergic Antagonists / Q000494:pharmacology*; D017209:Apoptosis; D006801:Humans; D008297:Male; D011470:Prostatic Hyperplasia / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011799:Quinazolines / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D018674:Adrenergic Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1