Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the insulin-like growth factor II autocrine growth loop.
Suramin is a polysulfonated naphthyl-urea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10(-4) and 9 x 10(-5) M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using 125I-IGF-I and found that suramin displaced 125I-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach.
Minniti
C P
CP
Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892.
Maggi
M
M
Helman
L J
LJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D017451:Receptors, Somatomedin; D012208:Rhabdomyosarcoma; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013498:Suramin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II