Procaine inhibits the erythroid differentiation of MEL cells by blocking commitment: possible involvement of calcium...

The action of procaine on the terminal erythroid differentiation of murine erythroleukemia (MEL) cells has been investigated at the level of individual cells. At concentrations (7 X 10-4 M) which had no inhibitory effect on cell growth, pretreatment of these cells with procaine for 12-24 hr caused a pronounced inhibition ( greater than 90%) of commitment of terminal erythroid differentiation of dimethyl sulfoxide (DMSO)-treated cells. Simultaneous treatment of MEL cells with DMSO and procaine, however, resulted to only slight inhibition (less than 20%) of commitment. Blockade of commitment by procaine pretreatment appears to be general since it was observed in cells treated with other inducers (6-thioguanine, dimethylformamide). Procaine pretreatment did not abolish the ability of MEL cells to complete the "latent period" and commit upon the removal of the block. Reversal of procaine inhibition of commitment was obtained by the addition of either CaCl2 (1.0 mM), calcium ionophore A23817 (1 microgram/ml), but not of MgCl2 (1.0 mM). From these data we conclude that procaine inhibits the terminal erythroid differentiation of MEL cells by blocking an event or process required for commitment which occurs prior to commitment itself. Our results suggest that this process involves calcium metabolism.