RAPID ALTERATION OF C-MYC AND C-JUN EXPRESSION IN LEUKEMIC-CELLS INDUCED TO DIFFERENTIATE BY A BUTYRIC-ACID PRODRUG

The novel prodrug of butyric acid (BA), pivaloyloxymethyl butyrate, ha s been shown, in vitro, to induce differentiation and inhibit leukemic cell proliferation. The prodrug affects the cells in vitro at lower c oncentration and at least 100 times faster than does (BA). We have com pared the ability of BA with that of its prodrug AN-9 to modulate the expression of the early regulating genes, c-myc and c-jun, in HL-60 ce lls. Exposure of HL-60 cells to the prodrug resulted in a decrease of c-myc and an increase of c-jun expression. The prodrug elicited this e ffect at lower concentrations and at least 100 times faster than BA. S ince changes in the expression of c-myc and c-jun occur minutes after exposure of the cells to the prodrug, these genes are likely to play a major role in the early stages of the differentiation pathway.