Hemin enhances the sensitivity of erythroleukemia cells to 1-beta-D-arabinofuranosylcytosine by both activation of deoxycytidine kinase and reduction of cytidine deaminase activity.
The sensitivity of human myelogenous leukemia cells to 1-beta-D-arabinofuranosylcytosine (ara-C) during induction of differentiation was examined. Treatment with hemin greatly increased the sensitivity of erythroid leukemia cells to ara-C. The enhancement of ara-C sensitivity by hemin was not as remarkable in nonerythroid leukemia cells. Hemin altered the metabolism of ara-C in human erythroleukemia K562 cells by reducing ara-C deaminase activity, increasing intracellular accumulation of ara-C, and activating the nucleoside kinases. These alterations may be involved in the enhancing effect of hemin on sensitivity of ara-C. These results suggest that some inducers of differentiation potentiate the antileukemic effect of ara-C on human erythroleukemia cells.
Honma
Y
Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Onozuka
Y
Y
Okabe-Kado
J
J
Kasukabe
T
T
Hozumi
M
M
D002454:Cell Differentiation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D003564:Cytidine Deaminase / Q000378:metabolism*; D003842:Deoxycytidine Kinase / Q000096:biosynthesis*; D004361:Drug Tolerance; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D019833:Genistein; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D007529:Isoflavones; D003561:Cytarabine; D006427:Hemin; D019833:Genistein; D003842:Deoxycytidine Kinase; D011505:Protein-Tyrosine Kinases; D003564:Cytidine Deaminase