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.