SURAMIN INHIBITS GROWTH AND TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) BINDING IN OSTEOSARCOMA CELL-LINES

Autocrine production of growth factors has been shown to be involved i n the multistep process of tumorigenesis. The ability of suramin, a po lyanionic anti-parasitic drug, to block growth factor-induced cell pro liferation makes it a potential antineoplastic drug. We studied the ef fects of suramin on seven osteosarcoma cell lines. Using clinically ac hievable concentrations of suramin (50-400 mu g/ml), we found a time- and dose-dependent inhibition of [H-3]thymidine incorporation. We also showed that suramin is able, dose-dependently, to prevent binding of transforming growth factor (TGF)-beta 1 to its receptors. DNA synthesi s inhibition by suramin was attenuated by TGF-beta 1 in some cell line s. Two cell lines that were inhibited by TGF-beta 1 were affected simi larly by suramin as cell lines that were stimulated by TGF-beta 1. In conclusion, in five out of seven osteosarcoma cell lines, we showed a correlation between inhibition of growth factor-stimulated mitogenesis and binding of TGF-beta 1 to its receptor. Similar effects in TGF-bet a 1-inhibited osteosarcoma cell lines suggest involvement of other mec hanisms and/or growth factors. However, suramin proves to be a potent inhibitor of osteosarcoma cell proliferation in vitro.