Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane

Abstract

The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [3H]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 micrograms ml-1. bFGF antisense oligomer (10 microM) reduced [3H]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 micrograms was a more potent inhibitor of angiogenesis than the combination of heparin 60 micrograms/hydrocortisone 50 micrograms; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (- 35 and - 29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone. Images Figure 1 Figure 4

Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects

“…Verification of this assay system is supported by our data showing VEGF significantly increased angiogenesis in this assay while suramin inhibited angiogenesis by approximately 50%. Suramin is an established anti-angiogenic agent and has been used to treat patients with various cancers (Stein et al, 1989;Danesi et al, 1993;Small et al, 2000). Therefore, the anti-angiogenic potency of these compounds suggests that they may be of improved therapeutic value.…”

Inhibition of Neutrophil Serine Proteinases by Suramin

“…Its use in acquired immunodeficiency syndrome was based on its potential inhibition of retroviral reverse transcriptase (9) and on its ability to decrease the binding of human immunodeficiency virus to T cells (10). The polysulfate is thought to exert its anti-tumoral action by impairing the binding of growth factors to the surface receptors of malignant cells (11,12) and by inhibiting angiogenesis (13). It may also have anti-invasive properties, due to the inhibition of heparanases (1).…”

Heparin-Like Drugs with Antiangiogenic Activity

“…The evolution of heparin-like synthetic drugs started in the early 90's. A polysulfonated naphthylurea (Suramin) was investigated in the inhibition of different proangiogenic factors (Danesi et al, 1993;Gagliardi et al, 1992). Based on the structure of suramin, different polysulfated and polysulfonic acid polymers were developed with capacity to interact with proangiogenic factors in similar mode to heparin (Fernández-Tornero et al, 2003;Liekens et al, 1999;Liekens et al, 1997).…”