Effects of Transferrin-Indium on Cellular Proliferation of a Human Leukemia Cell Line1

In previous studies, we have demonstrated that transferrin-gallium inhibits cellular proliferation by a mechanism whereby cellular iron utilization is impaired. Since indium, a similar class 3A metal, has not been well studied, we examined its effects on cellular iron uptake and cellular proliferation. In these studies, we provide evidence that indium, when bound to transferrin, has a 50-fold higher effect on inhibition of cellular proliferation than indium added as indium salt. Cells exposed to relatively low concentrations of transferrin-indium exhibit markedly in creased transferrin receptor expression but, as with transferrin-gallium, these cells incorporate an inappropriately low amount of iron, suggesting that there is a defect in the release of internalized iron from transferrin. In further studies, we utilize a monoclonal antibody against transferrin receptor that inhibits transfemn-mediated iron uptake. This antibody exhibits a dose-related inhibition of cellular proliferation, and when both transferrin-indium and monoclonal antibody are added to media, there is a more than additive effect on inhibition of cellular proliferation.