Combination of dasatinib and okadaic acid induces apoptosis and cell cycle arrest by targeting protein phosphatase PP2A in chronic myeloid leukemia cells

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dc.contributor.authorOzel, Buket
dc.contributor.authorKipcak, Sezgi
dc.contributor.authorAvci, Cigir Biray
dc.contributor.authorGunduz, Cumhur
dc.contributor.authorSaydam, Guray
dc.contributor.authorAktan, Cagdas
dc.contributor.authorGunel, Nur Selvi
dc.date.accessioned2024-03-13T10:30:52Z
dc.date.available2024-03-13T10:30:52Z
dc.date.issued2022
dc.departmentİstanbul Beykent Üniversitesien_US
dc.description.abstractChronic myeloid leukemia (CML) is a cancer type of the white blood cells and because of BCR-ABL translocation it results in increased tyrosine kinase activity. For this purpose, dasatinib is the second-generation tyrosine kinase inhibitor that is used for inhibition of BCR-ABL. Effectively and safetly, dasatinib has been used for imatinib-intolerant/resistant CML patients. Protein phosphatase 2A (PP2A) is the major serine/threonine phosphatase ensuring cellular homeostasis in cells and is associated with many cancer types including leukemias. In this study, we aimed to investigate the effects of dasatinib and okadaic acid (OA), either alone or in combination, on apoptosis and cell cycle arrest and dasatinib effect on enzyme activity and protein-level changes of PP2A in K562 cell line. The cytotoxic effects of dasatinib were evaluated by WST-1 analysis. Apoptosis was determined by Annexin V and Apo-Direct assays by flow cytometry. Cell cycle arrest analysis was performed for the investigation of the cytostatic effect. We also used OA as a PP2A inhibitor to assess apoptosis and cell cycle arrest changes in case of reducing the level of PP2A. PP2A enyzme activity and protein levels of PP2A were examined by serine/threonine phosphatase assay and Western blot analysis, respectively. Apoptosis was increased with dasatinib and OA combination. Cell cycle arrest was determined especially after OA treatment. The enzyme activity was decreased depending on time after dasatinib application. PP2A regulatory and catalytic subunit protein levels were decreased compared to control. Targeting the PP2A by dasatinib and OA has potential for CML treatment.en_US
dc.description.sponsorshipEge University Scientific Research Projects Fund (BAP) [2015-TIP-007]en_US
dc.description.sponsorshipThis study was financially supported by Ege University Scientific Research Projects Fund (BAP) which is Grant Number 2015-TIP-007.en_US
dc.identifier.doi10.1007/s12032-021-01643-2
dc.identifier.issn1357-0560
dc.identifier.issn1559-131X
dc.identifier.issue4en_US
dc.identifier.pmid35092492en_US
dc.identifier.scopus2-s2.0-85123875893en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1007/s12032-021-01643-2
dc.identifier.urihttps://hdl.handle.net/20.500.12662/3575
dc.identifier.volume39en_US
dc.identifier.wosWOS:000748321100008en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherHumana Press Incen_US
dc.relation.ispartofMedical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPP2Aen_US
dc.subjectOkadaic aciden_US
dc.subjectDasatiniben_US
dc.subjectChronic myeloid leukemiaen_US
dc.titleCombination of dasatinib and okadaic acid induces apoptosis and cell cycle arrest by targeting protein phosphatase PP2A in chronic myeloid leukemia cellsen_US
dc.typeArticleen_US

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