Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/4940
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dc.contributor.authorBaran, Yusuf-
dc.contributor.authorBielawski, Jacek-
dc.contributor.authorGündüz, Ufuk-
dc.contributor.authorÖğretmen, Besim-
dc.date.accessioned2017-03-01T13:26:11Z-
dc.date.available2017-03-01T13:26:11Z-
dc.date.issued2011-10-
dc.identifier.citationBaran, Y., Bielawski, J., Gündüz, U., and Öğretmen, B. (2011). Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation. Journal of Cancer Research and Clinical Oncology, 137(10), 1535-1544. doi:10.1007/s00432-011-1016-yen_US
dc.identifier.issn0171-5216-
dc.identifier.issn1432-1335-
dc.identifier.urihttp://doi.org/10.1007/s00432-011-1016-y-
dc.identifier.urihttp://hdl.handle.net/11147/4940-
dc.description.abstractPurpose: Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0.2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively. Methods: Cytotoxic effects of PDMP and imatinib were determined by XTT cell proliferation assay. Expression levels of GCS were determined by RT-PCR and western blot. Intracellular ceramide levels were determined by LC-MS. Cell viability analyses was conducted by Trypan blue dye exclusion assay. Cell cycle and apoptosis analyses were examined by flow cytometry. Results: We first showed that mRNA and protein levels of GCS are increased in drug-resistant K562/IMA as compared to sensitive K562 cells. Next, forced expression of GCS in sensitive K562 cells conferred resistance to imatinib-induced apoptosis. In reciprocal experiments, targeting GCS using its known inhibitor, PDMP, enhanced ceramide accumulation and increased cell death in response to imatinib in K562/IMA cells. Conclusion: Our data suggest the involvement of GCS in resistance to imatinib-induced apoptosis, and that targeting GCS by PDMP increased imatinib-induced cell death in drug-sensitive and drug-resistant K562 cells via enhancing ceramide accumulation.en_US
dc.description.sponsorshipNational Institutes of Health to BO (CA-088932, DE-016572, and CA097132)en_US
dc.language.isoenen_US
dc.publisherSpringer Verlagen_US
dc.relation.ispartofJournal of Cancer Research and Clinical Oncologyen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectApoptosisen_US
dc.subjectCeramideen_US
dc.subjectCMLen_US
dc.subjectDrug resistanceen_US
dc.subjectGlucosylceramideen_US
dc.titleTargeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulationen_US
dc.typeArticleen_US
dc.authoridTR119193en_US
dc.institutionauthorBaran, Yusuf-
dc.departmentİzmir Institute of Technology. Molecular Biology and Geneticsen_US
dc.identifier.volume137en_US
dc.identifier.issue10en_US
dc.identifier.startpage1535en_US
dc.identifier.endpage1544en_US
dc.identifier.wosWOS:000295988800016en_US
dc.identifier.scopus2-s2.0-80054726983en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1007/s00432-011-1016-y-
dc.identifier.pmid21833718en_US
dc.relation.doi10.1007/s00432-011-1016-yen_US
dc.coverage.doi10.1007/s00432-011-1016-yen_US
dc.identifier.wosqualityQ2-
dc.identifier.scopusqualityQ1-
item.openairetypeArticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.cerifentitytypePublications-
crisitem.author.dept04.03. Department of Molecular Biology and Genetics-
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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