Circulation · 1996
New activity of spironolactone. Inhibition of angiogenesis in vitro and in vivo.
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Klauber N, Browne F, Anand-Apte B, D'Amato R J
Аннотация
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.
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.
Предметные рубрики MeSH
AnimalsCattleCell DivisionCells, CulturedChemotaxisChick EmbryoCorneaEndothelial Growth FactorsEndothelium, VascularExtraembryonic MembranesFibroblast Growth Factor 2HumansLymphokinesMineralocorticoid Receptor AntagonistsNeovascularization, PathologicPlasminogen ActivatorsRabbitsSpironolactoneTissue Plasminogen ActivatorUrokinase-Type Plasminogen ActivatorVascular Endothelial Growth Factor AVascular Endothelial Growth Factors