Foscarnet reduces FGF2-induced proliferation of human umbilical vein endothelial cells and has antineoplastic activity against human anaplastic thyroid carcinoma cells

In contrast to many reports dealing with inhibitors of growth factor receptors like VEGF or FGFR, only few reports of low molecular weight inhibitors, which are directed against growth factors itself, are known. Here, foscarnet, an antiviral drug which inhibits several viral DNA polymerases by mimic pyrophosphate of nucleotides, was identified to interact with fibroblast growth factor 2 and stabilize the growth factor against tryptic digestion similar like the non-nitrogen containing bisphosphonates clodronate and etidronate that we have reported just recently as inhibitors of FGF-induced cell proliferation. Foscarnet competes with ATP against the binding on fibroblast growth factor 2 at the heparin/ATP-binding domain. This indicates binding of foscarnet at the heparin-binding domain of FGF2. This interaction of foscarnet with fibroblast growth factor 2 reduces FGF2-induced proliferation of human umbilical vein endothelial cells and intracellular signaling via ERK1/2 kinases in this cell line. Additionally, foscarnet reduces in a dose-dependent manner proliferation of CAL-62 cells that belong to anaplastic thyroid carcinoma, a rare but lethal type of thyroid cancer that expresses FGF2.