Induction of HL60 cell differentiation by tiazofurin and its analogues:
characterization and efficacy
BM Goldstein, JF Leary, BA Farley, VE Marquez, PC Levy and PT Rowley
Department of Biophysics, University of Rochester School of Medicine, NY
14642.
Among inducers of myeloid differentiation for leukemic cells, tiazofurin is
of special interest because its mechanism of action is known; it inhibits
inosine monophosphate dehydrogenase and thus decreases the guanine
nucleotide pool. Reported here are three aspects of tiazofurin induction of
myeloid differentiation in HL60 human acute promyelocytic leukemia cells.
First, inductive efficacy was evaluated for analogues ara-tiazofurin,
xylo-tiazofurin, and selenazofurin, for dinucleotide anabolites
thiazole-4-carboxamide adenine dinucleotide (TAD) and
selenazole-4-carboxamide adenine dinucleotide (SAD), and for a
phosphodiesterase-resistant TAD analogue, beta-methylene TAD. The results
showed that the parent compounds are more effective inducers than the
dinucleotide derivatives and that the selenazole analogues are more
effective inducers than the thiazole compounds. Second, HL60 cell induction
by tiazofurin was shown to be synergistic with that produced by the
antiviral agent ribavirin. Finally, tiazofurin was found to induce
expression of a phosphatidylinositol-specific phospholipase C- sensitive Fc
gamma-receptor III (FcRIII) on HL60 cells, a feature consistent with
neutrophilic, but not monocytic, differentiation.
Volume 78,
Issue 3,
pp. 593-598,
08/01/1991
Copyright © 1991 by The American Society of Hematology
