EFFECT OF NEPLANOCIN-A ON DIFFERENTIATION, NUCLEIC-ACID METHYLATION, AND C-MYC MESSENGER-RNA EXPRESSION IN HUMAN PROMYELOCYTIC LEUKEMIA-CELLS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 28  (1) , 45-50
Abstract
The effect of the cyclopentenyl adenosine analog neplanocin A (NPC) on cell growth and differentiation was examined in the human promyelocytic leukemia cell line HL-60. Continous exposure of HL-60 cells to 0.1-3.3 .mu.M NPC resulted in a progressive reduction in cell growth which was accompanied by an increase in differentiation to cells with a myelocyte and neutrophil morphology. The latter effect was expressed as an increase in the capacity of cells to reduce nitroblue tetrazolium and reached a level of 40% of the total cell population. Preceding the phenotypic changes was the preferential inhibition of RNA and DNA methylation in comparison to inhibition of their synthesis which coincided with the formation of a metabolite of NPC with the chromatographic characteristics of S-adenosyl-L-methionine (AdoMet). In addition, c-myc mRNA expression, which is amplified in HL-60 cells, was markedly reduced following NPC treatment. NPC is an effective inhibitor of RNA and DNA methylation resulting from its conversion to an analog of AdoMet, and these effects appear to be responsible for reduced c-myc RNA expression and the induction of myeloid differentiation in this cell line.