NEW ACTIVITY OF SPIRONOLACTONE - INHIBITION OF ANGIOGENESIS IN-VITRO AND IN-VIVO

Background The formation of new blood vessels (angiogenesis) is a crit ical component in a variety of pathological settings, including solid tumor growth, macular degeneration, and atherosclerosis. Methods and R esults We have found that orally administered spironolactone inhibited the area of angiogenesis induced by basic fibroblast growth factor (b FGF) in a rabbit corneal mi cropocket assay. Additionally, spironolact one inhibited bFGF- and vascular endothelial growth factor-stimulated capillary endothelial cell proliferation in vitro, inhibited bFGF-stim ulated capillary endothelial cell chemotaxis in vitro, and caused avas cular zones when placed on the chick chorioallantoic membrane. Experim ents analyzing spironolactone metabolites revealed that the major huma n metabolites 6 beta-hydroxy-7 alpha-thiomethyl spironolactone and can renoic acid retained antiangiogenic activity. The antiangiogenic activ ity appears to be unrelated to the antiandrogenic and antimineralocort icoid effects of spironolactone. Conclusions These experiments hold pr omise for the potential use of spironolactone as an orally administere d drug for the treatment of many diverse diseases dependent on angioge nesis.