Hemin enhances the sensitivity of erythroleukemia cells to 1-beta-D-arabinofuranosylcytosine by both activation of deoxycytidine kinase and reduction of cytidine deaminase activity.

Abstract

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.

• Authors: Y Honma, Y Onozuka, J Okabe-Kado, T Kasukabe, M Hozumi
• Journal: Cancer research (Cancer Res) Vol. 51 Issue 17 Pg. 4535-8 (Sep 01 1991) ISSN: 0008-5472 [Print] United States
• PMID: 1873797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoflavones
• Cytarabine
• Hemin
• Genistein
• Deoxycytidine Kinase
• Protein-Tyrosine Kinases
• Cytidine Deaminase

Topics

• Cell Differentiation (drug effects)
• Cytarabine (pharmacology)
• Cytidine Deaminase (metabolism)
• Deoxycytidine Kinase (biosynthesis)
• Drug Tolerance
• Enzyme Activation (drug effects)
• Erythrocytes (drug effects)
• Genistein
• Hemin (pharmacology)
• Humans
• Isoflavones (pharmacology)
• Leukemia, Erythroblastic, Acute (drug therapy, enzymology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Tumor Cells, Cultured (drug effects, enzymology)