Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells.
The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.
Pollak
M
M
Department of Medicine, McGill University, Montreal, PQ, Canada.
Richard
M
M
D000345:Affinity Labels; D000418:Albumins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000037:antagonists & inhibitors*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000345:Affinity Labels; D000418:Albumins; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D013498:Suramin; D007334:Insulin-Like Growth Factor I