Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells.
Suramin, a polyanionic compound, has previously been shown to dissociate platelet-derived growth factor (PDGF) from its receptor. In the present study suramin was found to inhibit the growth of sparse cultures of AKR-2B cells in fetal bovine serum (FBS)-supplemented medium in a dose-dependent, reversible fashion. Suramin also inhibited the ability of FBS, transforming growth factor beta (TGF beta), heparin-binding growth factor type-2 (HBGF-2), and epidermal growth factor (EGF) to stimulate DNA synthesis in density-arrested cultures of AKR-2B cells. The inhibition of growth factor-stimulated mitogenicity was directly correlated to the dose of suramin required to inhibit the binding of 125I-labeled TGF beta, HBGF-2, and EGF to their cell surface receptors. Suramin affected TGF beta and HBGF-2-related events at a 10-15-fold lower dose than that required for EGF-related events. It was also noted that suramin inhibited TGF beta-stimulated soft agar colony formation of AKR-2B (clone 84A) cells as well as the spontaneous colony formation of AKR-MCA cells, a chemically transformed derivative of AKR-2B cells. This demonstrates that suramin's spectrum of action for growth factors and their receptors should be extended to include TGF beta, HBGF-2, and EGF as well as PDGF. The data further suggest that the spontaneous growth of AKR-MCA cells in soft agar is dependent on growth factor binding to cell surface receptors.
D000362:Agar; D000818:Animals; D001769:Blood; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2; D006133:Growth Substances / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010455:Peptides / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology*; D015291:Transforming Growth Factors
D006133:Growth Substances; D010455:Peptides; D011986:Receptors, Somatotropin; D016222:Fibroblast Growth Factor 2; D013498:Suramin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D000362:Agar; D006493:Heparin