RT Journal Article
SR Electronic
T1 Effect of neplanocin A on differentiation, nucleic acid methylation, and c-myc mRNA expression in human promyelocytic leukemia cells.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 45
OP 50
VO 28
IS 1
A1 J Linevsky
A1 M B Cohen
A1 K D Hartman
A1 M C Knode
A1 R I Glazer
YR 1985
UL http://molpharm.aspetjournals.org/content/28/1/45.abstract
AB 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. Continuous exposure of HL-60 cells to 0.1-3.3 microM 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 nitro blue 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. These results indicate that NPC is an effective inhibitor of RNA and DNA methylation resulting from its conversion to an analog of AdoMet, and that these effects appear to be responsible for reduced c-myc RNA expression and the induction of myeloid differentiation in this cell line.