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, has been shown, in vitro, to induce differentiation and inhibit leukemic cell proliferation. The prodrug affects the cells in vitro at lower concentration and at least 100 times faster than does (BA). We have compared 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 cells. 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 effect at lower concentrations and at least 100 times faster than BA. Since 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.