Effect of suramin on 125I-insulin-like growth factor-I binding to human meningiomas and on proliferation of meningioma cells.
Suramin, a polyanionic compound, has been shown to inhibit the binding of various growth factors to cell surface receptors. The effects of suramin on 125I-insulin-like growth factor (IGF)-I binding to human meningioma tissues and IGF-I-induced deoxyribonucleic acid (DNA) synthesis in cultured meningioma cells were examined using the quantitative receptor autoradiographic method and 3H-thymidine incorporation, respectively. Suramin inhibited specific 125I-IGF-I binding to meningioma tissue sections in concentration-dependent manner, with a 50% inhibiting concentration (IC50) of 8.7 +/- 0.5 x 10(-5) M. The addition of 10(-3) M suramin to the incubation buffer potently dissociated 125I-IGF-I previously bound to meningioma tissue as a function of time (dissociation half-life (T1/2) 6.8 minutes). After preincubation of tissue sections with 10(-3) M suramin for 120 minutes, there was no inhibition of the subsequent 125I-IGF-I binding to meningiomas. Suramin inhibited the IGF-I-induced incorporation of 3H-thymidine into meningioma cells in a dose-dependent manner, with an IC50 of 4.6 +/- 1.4 x 10(-5) M. The growth rate of meningioma cells (determined 4 days after seeding) was reduced by 10%, 20%, and 50% of the control culture in the presence of 10(-6), 10(-5), and 10(-4) M suramin, respectively. These results suggest that suramin interferes with IGF-I binding to meningioma tissue and inhibits proliferation of cells, at least partially by preventing IGF-I-induced DNA synthesis and probably by interacting with IGF-I directly rather than with its binding sites.
Tsutsumi
K
K
Department of Neurosurgery, Nagasaki University School of Medicine, Japan.
Kitagawa
N
N
Niwa
M
M
Himeno
A
A
Taniyama
K
K
Shibata
S
S
D000368:Aged; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D013498:Suramin; D007334:Insulin-Like Growth Factor I