BUTYRIC-ACID AND ITS MONOSACCHARIDE ESTER INDUCE APOPTOSIS IN THE HL-60 CELL-LINE

Butyric acid is a potent cell growth inhibitor and differentiation inducer. However, the short plasma half-life of this fatty acid limits its potential therapeutic use. The recent synthesis of several monosaccharide esters of butyric sodium salt (BuONa) with a prolonged plasma half-life and similar biological properties as the sodium salt opens new perspectives. We report here that the human myeloid HL-60 cell line can be induced to apoptosis when cultured with one of these esters, monoacetone glucose 3-butyrate (MAG = 3but) or BuONa. Cytospin slide preparations and flow cytometric studies showed that HL-60 cells treated with 1 mM MAG = 3but or BuONa exhibited a reduction in cell volume and condensation of nuclear structure characteristic of apoptosis, associated with monocytic differentiation. Time course studies demonstrated that DNA fragmentation, as determined by agarose gel electrophoresis, was detected 4 hours after incubation with the drugs, while morphologic signs appeared at day 3. Apoptotic cells increased with culture time and reached a maximum at day 6 of 20 ± 5% with BuONa, 25 ± 5% with MAG = 3but, and only 5 ± 2% in controls. These findings suggest that these drugs may exert their actions, at least in part, through induction of apoptosis. © 1993 Acdamic Press. Inc.