Induction of human leukemia cell differentiation by regiospecifically acetylated spermidines

The activity of two naturally occurring monoacetylated polyamines, N8-acetylspermidine and N1-acetylspermidine, as inducers of differentiation of HL60 human leukemia cells was assessed. Differentiation was quantified by morphological changes and the ability to reduce nitroblue tetrazolium. N8-Acetylspermidine produced 25-35 percent differentiation at 3 microM and 80-90 percent differentiation at 15 microM. Higher concentrations caused cell death. Cell growth was inhibited by N8-acetylspermidine at 3.8 microM. No differentiation activity or inhibition of cell growth was found with N1-acetylspermidine at concentrations up to 1.2 mM. The observed dependence of activity on the position of the acetyl group on monoacetylspermidine is in contrast to the broad structural specificity of known inducers of HL60 cell differentiation.