Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells
The Korean Journal of Internal Medicine
;
: 357-366, 2016.
Article
in English
| WPRIM
| ID: wpr-109562
ABSTRACT
BACKGROUND/AIMS:
The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies.METHODS:
We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib.RESULTS:
Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib-resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr-Abl, nuclear factor-kappaB (NF-kappaB) and beta-catenin.CONCLUSIONS:
We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappaB and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Triazoles
/
Benzoates
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
Signal Transduction
/
Iron Chelating Agents
/
Apoptosis
/
Drug Resistance, Neoplasm
/
K562 Cells
/
Protein Kinase Inhibitors
/
Cell Proliferation
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2016
Type:
Article
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