title: Apoptosis induction by doxazosin and other quinazoline alpha1-adrenoceptor antagonists: a new mechanism for cancer treatment?
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.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Vaughan
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D017292:Doxazosin / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D011799:Quinazolines; D017292:Doxazosin