Trimidox-mediated morphological changes during erythroid differentiation is associated with the stimulation of hemoglobin and F-cell production in human K562 cells.
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.
Iyamu
E W
EW
Comprehensive Sickle Cell Center, Nashville, Tennessee 37208, USA.
Adunyah
S E
SE
Elford
H L
HL
Fasold
H
H
Turner
E A
EA
D001550:Benzamidines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D005319:Fetal Hemoglobin / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
C074761:3,4,5-trihydroxybenzamidoxime; D001550:Benzamidines; D004791:Enzyme Inhibitors; D005319:Fetal Hemoglobin; D012264:Ribonucleotide Reductases