Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.
Suramin, an anticancer agent in current clinical trials, is a prototype of a pharmacological antagonist of growth factors, including basic fibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of heparin stimulated angiogenesis and counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC50) of suramin was determined for key cellular mechanisms that regulate angiogenesis: (a) low and high affinity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC50s, respectively, of 24.3 and 71.5 micrograms/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine aortic endothelial cells with IC50s of 200-320 micrograms/ml; (c) proliferation of bovine pulmonary artery endothelial cells at > 100 micrograms/ml and of BCE cells at > 250 micrograms/ml; and (d) urokinase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211 micrograms/ml and of BCE cells stimulated by bFGF at > 100 micrograms/ml, but not plasminogen activator activity induced by phorbol 12-myristate 13-acetate. Suramin inhibited multiple control points of angiogenesis, including those stimulated by bFGF. Because tumor growth is angiogenesis dependent, the clinical efficacy of suramin may relate, in part, to angiosuppression.
Takano
S
S
Division of Neurological Surgery, Northwestern Memorial Hospital and School of Medicine, Chicago, Illinois 60611-2906.
Gately
S
S
Neville
M E
ME
Herblin
W F
WF
Gross
J L
JL
Engelhard
H
H
Perricone
M
M
Eidsvoog
K
K
Brem
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D003315:Cornea / Q000098:blood supply; D004354:Drug Screening Assays, Antitumor; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004790:Enzyme Induction / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D016222:Fibroblast Growth Factor 2; D013498:Suramin; D014568:Urokinase-Type Plasminogen Activator