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Induction of prostate apoptosis by α1-adrenoceptor antagonists: mechanistic significance of the quinazoline component

Prostate Cancer and Prostatic Diseases volume 5, pages 88–95 (2002)Cite this article

Abstract

α1-Adrenoceptor antagonists, have been documented to induce apoptosis and reduce prostate tumor vascularity in benign and malignant prostate cells. The quinazoline based α1-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 α1-adrenoceptor independent mechanism potentially involving activation of the TGF-β signal transduction pathway. This review discusses the current knowledge of the action of quinazoline-derived α1-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.

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Acknowledgements

These studies were supported by educational grants from Pfizer Pharmaceuticals and Abbot International.

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  1. Division of Urology, Department of Surgery and Department of Molecular Biology and Biochemistry, University of Maryland School of Medicine, Baltimore, Maryland, USA

    I E Anglin, D T Glassman & N Kyprianou

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Correspondence to N Kyprianou.

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Anglin, I., Glassman, D. & Kyprianou, N. Induction of prostate apoptosis by α1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis 5, 88–95 (2002). https://doi.org/10.1038/sj.pcan.4500561

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