SELECTIVE INDUCTION OF APOPTOSIS IN MYELOID LEUKEMIC-CELL LINES BY MONOACETONE GLUCOSE-3 BUTYRATE

Butyric acid is a potent cell growth inhibitor and differentiation inducer. Our previous studies have shown that MAG=3but, a monosaccharide ester of butyric acid, used at 1 mM, induces apoptosis in the HL-60 cell line. We report here that this drug can also induce apoptosis in the U-937 leukemic cell lines whereas the myeloblastic KG1 and the NB4 promyelocytic leukemic cell lines were refractory to induction of apoptosis. In order to determine what can trigger cells to undergo apoptosis, cell cycle analysis, induction of differentiation and p53, c-myc and Bcl-2 expression was studied. Apoptosis was correlated to an arrest of cell growth in the G1 phase of the cell cycle and to an induction of differentiation through the monocytic pathway in HL-60 and U-937 cells. Time course studies demonstrated DNA fragmentation after few hours incubation with the drug, while morphological signs appeared later (days 2 or 3). Northern blot analysis and flow cytometric studies have shown that cell death induced by MAG=3but was not associated to an overexpression of c-myc and p53. However, in the HL-60 cells, BCL-2 protein expression was decreased after MAG=3but treatment, corroborating the apoptosis observed. (C) 1994 Academic Press, Inc.