Changes in polyamine catabolism in HL-60 human promyelogenous leukaemic cells in response to etoposide-induced apoptosis

Abstract

The topoisomerase II inhibitor etoposide induced apoptosis in HL-60 cells within 4 h of exposure to the drug, as measured by changes in morphology, DNA fragmentation and cytotoxicity assays. Etoposide-induced apoptosis was accompanied by an increase in polyamine efflux from the cells and a decrease in total polyamine content during the first 24 h of exposure to the drug. Although both enzyme activities increased slightly, there were no significant changes in spermidine/spermine N1-acetyltransferase activity or polyamine oxidase activity. After longer exposures (48–72 h), significant induction of spermidine/spermine N1-acetyltransferase activity and loss of polyamine content occurred. These results suggest that polyamine oxidation and the resultant hydrogen peroxide produced may be associated with the initiation of apoptosis, while induction of the acetyltransferase and overall loss of intracellular polyamines may be involved in the final, possibly necrotic, stages of cell death.