Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.

Abstract

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.

• Authors: S Takano, S Gately, M E Neville, W F Herblin, J L Gross, H Engelhard, M Perricone, K Eidsvoog, S Brem
• Journal: Cancer research (Cancer Res) Vol. 54 Issue 10 Pg. 2654-60 (May 15 1994) ISSN: 0008-5472 [Print] United States
• PMID: 7513254 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fibroblast Growth Factor 2
• Suramin
• Urokinase-Type Plasminogen Activator

Topics

• Animals
• Cell Division (drug effects)
• Cell Movement (drug effects)
• Chick Embryo
• Cornea (blood supply)
• Drug Screening Assays, Antitumor
• Endothelium, Vascular (drug effects, pathology)
• Enzyme Induction (drug effects)
• Fibroblast Growth Factor 2 (antagonists & inhibitors, metabolism)
• Male
• Neovascularization, Pathologic (prevention & control)
• Rats
• Rats, Wistar
• Suramin (pharmacology)
• Urokinase-Type Plasminogen Activator (biosynthesis)