Induction of differentiation of embryonal carcinoma F9 cells by iron chelators.

The effects of several chelators, including hinokitiol, on embryonal carcinoma F9 cell differentiation were assessed by assaying the production of plasminogen activator (PA) as a differentiation marker protein. Hinokitiol and tropolone which were potent differentiation inducers lost their activity following preincubation with Fe2+ and Fe3+ ions. Other metal ions had no or little effect on the hinokitiol-induced differentiation. Of several chelators examined, dithizone induced differentiation as effectively as did hinokitiol and tropolone. Dithizone-induced differentiation was also inhibited by preincubation with Fe3+ ions. It was concluded that some potent iron chelators could trigger the teratocarcinoma F9 cells to differentiate through the chelation with intracellular iron ions.