Apoptosis Induction by Doxazosin and Other Quinazoline Alpha1-adrenoceptor Antagonists: a New Mechanism for Cancer Treatment?

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2009 Nov 12

PMID 19904527

Citations 12

Authors

Natasha Kyprianou

Taylor B Vaughan

Martin C Michel

Affiliations

Soon will be listed here.

Abstract

Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require much high concentrations than those required for receptor occupancy. Several studies have invested efforts towards the elucidation of the molecular mechanisms underlying doxazosin-induced apoptosis. These include various tumor cells, cardiomyocytes, endothelial cells and bladder smooth muscle cells. While the high concentrations of doxazosin required to induce apoptosis challenge the use of this and related drugs for clinical optimization of apoptosis induction, such quinazoline structure may represent chemical starting points to develop more potent apoptosis-inducing agents free of alpha(1)-adrenoceptor antagonistic action and suitable for cancer treatment with minimal and well-tolerated side effects.

Citing Articles

Protective Effect of Curcumin against Doxazosin- and Carvedilol-Induced Oxidative Stress in HepG2 Cells.

Medina-Pizano M, Medina-Rosales M, Martinez-Hernandez S, Aldaba-Muruato L, Macias-Perez J, Sanchez-Aleman E Oxid Med Cell Longev. 2022; 2022:6085515.

PMID: 35189631 PMC: 8856820. DOI: 10.1155/2022/6085515.

Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy.

Wdowiak P, Matysiak J, Kuszta P, Czarnek K, Niezabitowska E, Baj T Front Chem. 2021; 9:765552.

PMID: 34805097 PMC: 8595829. DOI: 10.3389/fchem.2021.765552.

MH-76, a Novel Non-Quinazoline α-Adrenoceptor Antagonist, but Not Prazosin Reduces Inflammation and Improves Insulin Signaling in Adipose Tissue of Fructose-Fed Rats.

Kubacka M, Mogilski S, Zadrozna M, Nowak B, Szafarz M, Pomierny B Pharmaceuticals (Basel). 2021; 14(5).

PMID: 34069933 PMC: 8157569. DOI: 10.3390/ph14050477.

Label-Free Dynamic Mass Redistribution Reveals Low-Density, Prosurvival -Adrenergic Receptors in Human SW480 Colon Carcinoma Cells.

Harris D, Park J, Lee K, Xu C, Stella N, Hague C J Pharmacol Exp Ther. 2017; 361(2):219-228.

PMID: 28196836 PMC: 5399639. DOI: 10.1124/jpet.116.237255.

The Role of α1-Adrenoceptor Antagonists in the Treatment of Prostate and Other Cancers.

Batty M, Pugh R, Rathinam I, Simmonds J, Walker E, Forbes A Int J Mol Sci. 2016; 17(8).

PMID: 27537875 PMC: 5000736. DOI: 10.3390/ijms17081339.

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