Pleiotropic actions of suramin on the proliferation of human breast-cancer cells in vitro.

Suramin, a non-specific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breast-cancer 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 Evsa-T cells being by far the most sensitive ones. A suramin concentration of 100 micrograms/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 (EGF-R) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for T-47D and MDA-MB-231 cells. The non-specificity of the action of suramin was established by the observation that suramin-induced inhibition of cell proliferation could be abolished by insulin-like growth factor-I (IGF-I) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serum-free conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the non-specific 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.