Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors.

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Zugmaier G, Favoni R, Jaeger R, Rosen N, Knabbe C

Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors.

Ann N Y Acad Sci. 1999;886:243-8.

PubMed ID

10667230 [ View in PubMed

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Abstract

Angiogenesis is a prerequisite for tumor expansion and metastasis. The angiogenic potential of the heparin-binding growth factors acidic fibroblast growth factor (FGF) and basic FGF has been demonstrated in various publications. We studied the inhibitory effects of suramin and the polysulfated heparinoids pentosan polysulfate, dextran sulfate, and fucoidan on the action of FGF. As an experimental model, we used the adrenal cancer cell line SW 13, whose anchorage-independent growth depends on the presence of FGF. The polysulfated heparinoids inhibited FGF-induced growth and binding to the receptor at an IC50 of 0.5-3 micrograms/ml. Suramin inhibited FGF at an IC50 of 100 micrograms/ml. The polysulfated heparinoids exerted no effect on IGF-1 or TGF alpha-related growth. Suramin inhibited the anchorage-independent growth induced by IGF-1 or TGF alpha only at an IC50 of 100 micrograms/ml. Our results indicate that suramin inhibits growth factors in a nonselective way. By contrast, polysulfated heparinoids exert a selective inhibitory effect on heparin binding angiogenesis factors at an IC50, which is 100 times below the IC50 of suramin. Therefore, the administration of polysulfated heparinoids might become a novel approach to tumor therapy based on blocking angiogenesis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pentosan polysulfate	Fibroblast growth factor 2	Protein	Humans	Yes	Antagonist	Details