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Pleiotropic actions of suramin on the proliferation of human breast-cancer cells in vitro
Suramin, a nonâspecific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breastâcancer cell lines in vitro. In complete growth medium, pleiotropic effects were observed with respect to cell proliferation, i.e. suramin is stimulatory at low concentrations and inhibitory at higher concentrations, for 4 of the 6 cell lines studied. The various cell lines showed marked differences with respect to the antiproliferative action of suramin, the EvsaâT cells being by far the most sensitive ones. A suramin concentration of 100 ÎŒg/ml brought about a 100% stimulation of the proliferation of ZR/HERc cells, ZR 75.1 cells ectopically expressing a human epidermal growth factor receptor (EGFâR) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for Tâ47D and MDAâMBâ231 cells. The nonâspecificity of the action of suramin was established by the observation that suraminâinduced inhibition of cell proliferation could be abolished by insulinâlike growth factorâ1 (IGFâI) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serumâfree conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the nonâspecific nature of its action. The stimulatory effect of low concentrations of suramin on the proliferation of breast cancer cells may have important consequences for breast cancer patients treated with suramin. Copyrigh