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Trimidox-mediated morphological changes during erythroid differentiation is associated with the stimulation of hemoglobin and F-cell production in human K562 cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1998 Jun 29; Vol. 247 (3), pp. 759-64. - Publication Year :
- 1998
-
Abstract
- Trimidox (3,4,5-trihdroxybenzamidoxime) has been shown to reduce the activity of ribonucleotide reductase with accompanied growth inhibition and differentiation of mammalian cells. Hydroxyurea (HU) is the only ribonucleotide reductase inhibitor in clinical use for the treatment and management of sickle cell anemia, since this compound increases fetal hemoglobin (Hb F) production: a potent inhibitor of sickle hemoglobin (Hb SS) polymerization. However, the main limitations of HU is its lack of potency, myelosuppression and short half life. These studies investigated the effects of trimidox on the induction of hemoglobin and F-cells production in K562 erythroleukemia cells. Our study reveals that trimidox exhibits concentration dependent inhibitory effect on K562 cells with increase in benzidine positive normoblasts and F-cells production as well as morphological changes typical of erythroid differentiation. These findings provide the first evidence that the growth inhibitory differentiation of cells induced by trimidox enhance hemoglobin and F-cells production.
- Subjects :
- Cell Division drug effects
Enzyme Inhibitors
Erythroid Precursor Cells cytology
Erythroid Precursor Cells drug effects
Fetal Hemoglobin metabolism
Histocytochemistry
Humans
Leukemia, Erythroblastic, Acute metabolism
Tumor Cells, Cultured
Benzamidines pharmacology
Cell Differentiation drug effects
Ribonucleotide Reductases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 247
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 9647767
- Full Text :
- https://doi.org/10.1006/bbrc.1998.8534