Deferasirox shows in vitro and in vivo antileukemic effects on murine leukemic cell lines regardless of iron status.

Abstract

Numerous studies have shown the antiproliferative effect of iron chelating agents (ICAs), which have been used traditionally in patients with secondary iron overload (SIO). Because the in vivo model for these studies has been animals with normal iron status, the antileukemic effect of ICAs in the SIO condition has not been determined clearly. We investigated the in vitro and in vivo effects of ICAs in murine leukemic cell lines regarding the iron status. The viability of both EL4 cells and L1210 cells incubated with either deferoxamine (DFO) or deferasirox (DFX) decreased in a concentration-dependent manner. This effect was most prominent in L1210 cells treated with DFX. The viability of L1210 cells incubated with both ICAs did not change regardless of the presence of ferric chloride. The percentage of apoptosis in L1210 cells treated with DFO or DFX increased in a concentration-dependent manner; however, the expression of Fas showed no significant change. The non-SIO mice and SIO mice bearing L1210 cells showed longer survival than other groups when treated with DFX, whereas the SIO mice treated with DFO showed shorter survival than the control group. The tumor was significantly smaller in the SIO mice treated with DFX or DFO compared with the control group. The iron content of the liver or the tumor in SIO mice decreased after ICA treatment. This study indicates an antileukemic effect of DFX regardless of iron status and suggests that the use of DFX has a survival benefit for SIO leukemia murine model in terms of iron chelation and antileukemic therapy.

• Authors: Dae-Hyoung Lee, Pil Sang Jang, Nack Gyun Chung, Bin Cho, Dae Chul Jeong, Hack Ki Kim
• Journal: Experimental hematology (Exp Hematol) Vol. 41 Issue 6 Pg. 539-46 (Jun 2013) ISSN: 1873-2399 [Electronic] Netherlands
• PMID: 23415674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzoates
• Chlorides
• Fas protein, mouse
• Ferric Compounds
• Iron Chelating Agents
• Neoplasm Proteins
• Triazoles
• fas Receptor
• Iron-Dextran Complex
• Iron
• Deferoxamine
• ferric chloride
• Deferasirox

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Benzoates (pharmacology, therapeutic use)
• Cell Line, Tumor (drug effects)
• Chlorides (pharmacology)
• Crosses, Genetic
• Deferasirox
• Deferoxamine (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Ferric Compounds (pharmacology)
• Gene Expression Regulation, Leukemic (drug effects)
• Iron (metabolism)
• Iron Chelating Agents (pharmacology, therapeutic use)
• Iron Overload (chemically induced, complications)
• Iron-Dextran Complex (toxicity)
• Leukemia L1210 (complications, drug therapy, metabolism, pathology)
• Liver (metabolism)
• Lymphoma, T-Cell (metabolism, pathology)
• Mice
• Mice, Inbred Strains
• Neoplasm Proteins (biosynthesis, genetics)
• Triazoles (pharmacology, therapeutic use)
• Tumor Burden
• fas Receptor (biosynthesis, genetics)