BACKGROUND: The formation of new blood vessels (angiogenesis) is a critical component in a variety of pathological settings, including solid tumor growth, macular degeneration, and atherosclerosis. METHODS AND RESULTS: We have found that orally administered spironolactone inhibited the area of angiogenesis induced by basic fibroblast growth factor (bFGF) in a rabbit corneal micropocket assay. Additionally, spironolactone inhibited bFGF- and vascular endothelial growth factor-stimulated capillary endothelial cell proliferation in vitro, inhibited bFGF-stimulated capillary endothelial cell chemotaxis in vitro, and caused avascular zones when placed on the chick chorioallantoic membrane. Experiments analyzing spironolactone metabolites revealed that the major human metabolites 6 beta-hydroxy-7 alpha-thiomethyl spironolactone and canrenoic acid retained antiangiogenic activity. The antiangiogenic activity appears to be unrelated to the antiandrogenic and antimineralocorticoid effects of spironolactone. CONCLUSIONS: These experiments hold promise for the potential use of spironolactone as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
BACKGROUND: The formation of new blood vessels (angiogenesis) is a critical component in a variety of pathological settings, including solid tumor growth, macular degeneration, and atherosclerosis. METHODS AND RESULTS: We have found that orally administered spironolactone inhibited the area of angiogenesis induced by basic fibroblast growth factor (bFGF) in a rabbit corneal micropocket assay. Additionally, spironolactone inhibited bFGF- and vascular endothelial growth factor-stimulated capillary endothelial cell proliferation in vitro, inhibited bFGF-stimulated capillary endothelial cell chemotaxis in vitro, and caused avascular zones when placed on the chick chorioallantoic membrane. Experiments analyzing spironolactone metabolites revealed that the major human metabolites 6 beta-hydroxy-7 alpha-thiomethyl spironolactone and canrenoic acid retained antiangiogenic activity. The antiangiogenic activity appears to be unrelated to the antiandrogenic and antimineralocorticoid effects of spironolactone. CONCLUSIONS: These experiments hold promise for the potential use of spironolactone as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.
Authors: D Marshall Brinkley; Li Wang; Chang Yu; E Wilson Grandin; Michael S Kiernan Journal: J Heart Lung Transplant Date: 2021-09-09 Impact factor: 10.247
Authors: S H Slight; V K Chilakamarri; S Nasr; A K Dhalla; F J Ramires; Y Sun; V K Ganjam; K T Weber Journal: Mol Cell Biochem Date: 1998-12 Impact factor: 3.396
Authors: Francesco Di Fabio; Carlos Alvarado; Agnieszka Majdan; Adrian Gologan; Linda Voda; Elliot Mitmaker; Lenore K Beitel; Philip H Gordon; Mark Trifiro Journal: J Gastrointest Surg Date: 2007-08-17 Impact factor: 3.452
Authors: Mohamed Sabra; Catherine Karbasiafshar; Ahmed Aboulgheit; Sidharth Raj; M Ruhul Abid; Frank W Sellke Journal: Int J Mol Sci Date: 2021-04-02 Impact factor: 5.923