Induction of embryonal carcinoma cell differentiation by deferoxamine, a potent therapeutic iron chelator

We investigated the effects of deferoxamine on the differentiation of embryonal carcinoma F9 cells. Deferoxamine, a widely used therapeutic agent for thalassemia and iron overload, was found to induce F9 cell differentiation and to have some unique characteristics compared with other chelators, hinokitiol and dithizone, which were previously reported to induce differentiation of these cells. This hydrophilic agent induced reversible differentiation as did sodium butyrate, whereas other chelators did not. However, morphological features of the cells after deferoxamine-induced differentiation were similar to those of cells incubated with the other chelators. The differentiation-inducing activity of deferoxamine was abolished by preincubation with Fe3+ ions, similarly to the other chelators examined. Moreover, cell proliferation was inhibited by treatment with this agent, and the numbers of cells in the colonies were reduced by apoptosis. Based on these results, we conclude that deferoxamine induces differentiation and apoptosis of F9 cells via chelation of extracellular and/or intracellular Fe3+ ions.