LACK OF EFFECT OF CORTICOSTEROIDS AND TAMOXIFEN ON SURAMIN PROTEIN-BINDING AND IN-VITRO ACTIVITY

Stout and colleagues [Proc Am Assoc Cancer Res 1993, 34, p. 298] previ ously reported that both hydrocortisone and tamoxifen increased the fr ee fraction of suramin in human plasma. We examined several corticoste roids as well as tamoxifen for their effects on suramin protein bindin g and also evaluated hydrocortisone for its ability to modulate surami n activity in PC-3 and MCF-7 cells. Greater than 99% of the suramin wa s protein bound in undiluted human plasma. However, the free fraction of suramin was increased with the reduced plasma protein levels and in creased suramin concentrations. At concentrations ranging from 1 to 30 mu M, neither tamoxifen, hydrocortisone, prednisone nor dexamethasone had any effect on the binding of suramin to human plasma, regardless of protein concentrations. Similar results were observed with fetal ca lf serum. Hydrocortisone also had no effect on suramin activity agains t PC-3 and MCF-7 cell in vitro. We conclude from these studies that ne ither corticosteroids nor tamoxifen affect suramin protein binding or its cytotoxic activity.