title: New activity of spironolactone. Inhibition of angiogenesis in vitro and in vivo.
abstract: 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.
  
  
  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.affiliation: Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
authors.forename: N
authors.initials: N
authors.lastname: Klauber
authors.forename: F
authors.initials: F
authors.lastname: Browne
authors.forename: B
authors.initials: B
authors.lastname: Anand-Apte
authors.forename: R J
authors.initials: RJ
authors.lastname: D'Amato
mesh_terms: D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002642:Chick Embryo; D003315:Cornea / Q000098:blood supply; D016228:Endothelial Growth Factors; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005321:Extraembryonic Membranes / Q000098:blood supply; D016222:Fibroblast Growth Factor 2; D006801:Humans; D008222:Lymphokines; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D010960:Plasminogen Activators / Q000378:metabolism; D011817:Rabbits; D013148:Spironolactone / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D000451:Mineralocorticoid Receptor Antagonists; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013148:Spironolactone; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator