Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells
DC Field | Value | Language |
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dc.contributor.author | Kim, Dae Sik | - |
dc.contributor.author | Na, Yoo Jin | - |
dc.contributor.author | Kang, Myoung Hee | - |
dc.contributor.author | Yoon, Soo-Young | - |
dc.contributor.author | Choi, Chul Won | - |
dc.date.accessioned | 2021-09-04T02:21:15Z | - |
dc.date.available | 2021-09-04T02:21:15Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2016-03 | - |
dc.identifier.issn | 1226-3303 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/89443 | - |
dc.description.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 Bcr-Abl, phosphorylated Bcr-Abl, nuclear factor-kappa B (NF-kappa B) 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-kappa B 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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | KOREAN ASSOC INTERNAL MEDICINE | - |
dc.subject | KAPPA-B PATHWAY | - |
dc.subject | BCR-ABL | - |
dc.subject | TYROSINE KINASE | - |
dc.subject | BETA-CATENIN | - |
dc.subject | HEMATOLOGICAL MALIGNANCIES | - |
dc.subject | MOLECULAR-MECHANISMS | - |
dc.subject | STEM-CELLS | - |
dc.subject | INHIBITOR | - |
dc.subject | CANCER | - |
dc.subject | CHEMOTHERAPY | - |
dc.title | Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Dae Sik | - |
dc.contributor.affiliatedAuthor | Yoon, Soo-Young | - |
dc.contributor.affiliatedAuthor | Choi, Chul Won | - |
dc.identifier.doi | 10.3904/kjim.2015.024 | - |
dc.identifier.scopusid | 2-s2.0-84960116519 | - |
dc.identifier.wosid | 000372174600017 | - |
dc.identifier.bibliographicCitation | KOREAN JOURNAL OF INTERNAL MEDICINE, v.31, no.2, pp.357 - 366 | - |
dc.relation.isPartOf | KOREAN JOURNAL OF INTERNAL MEDICINE | - |
dc.citation.title | KOREAN JOURNAL OF INTERNAL MEDICINE | - |
dc.citation.volume | 31 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 357 | - |
dc.citation.endPage | 366 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002089203 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | General & Internal Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, General & Internal | - |
dc.subject.keywordPlus | KAPPA-B PATHWAY | - |
dc.subject.keywordPlus | BCR-ABL | - |
dc.subject.keywordPlus | TYROSINE KINASE | - |
dc.subject.keywordPlus | BETA-CATENIN | - |
dc.subject.keywordPlus | HEMATOLOGICAL MALIGNANCIES | - |
dc.subject.keywordPlus | MOLECULAR-MECHANISMS | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | INHIBITOR | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordAuthor | Deferasirox | - |
dc.subject.keywordAuthor | Iron chelator | - |
dc.subject.keywordAuthor | Chronic myeloid leukemia | - |
dc.subject.keywordAuthor | Imatinib | - |
dc.subject.keywordAuthor | Resistance | - |
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