Prolonged Β-Hydroxybutyrate-Mediated Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells

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dc.authoridAli Burak Özkaya / 0000-0002-4811-2082
dc.authoridSenanur Malcanlı / 0000-0003-3811-8146
dc.authoridÖykü Gönül Geyik / 0000-0003-3014-1253
dc.authorscopusidÖykü Gönül Geyik / 57221379876
dc.authorwosidÖykü Gönül Geyik / AHB-4716-2022
dc.contributor.authorÖzkaya, Ali Burak
dc.contributor.authorMalcanlı, Senanur
dc.contributor.authorGeyik, Öykü Gönül
dc.date.accessioned2025-04-17T08:58:21Z
dc.date.available2025-04-17T08:58:21Z
dc.date.issued31 Ocak 2025
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü
dc.description.abstractPurpose: Ketosis is a metabolic state characterized by production of ketone bodies, including acetoacetate, β-hydroxybutyrate (BHB), and acetone, in response to reduced blood glucose levels. BHB stands out as the principal ketone body in nutritional ketosis which has diverse therapeutic implications for metabolic, nondegenerative and neoplastic disorders. In current study we investigated the impact of ketosis on chronic myeloid leukaemia (CML) cell viability and drug response. Materials and Methods: We investigated the impact of BHB-mediated ketosis on the viability of K562 cells, an in vitro model of CML, and explored the influence of BHB on the sensitivity of these cells to ponatinib, a multi-targeted tyrosine kinase inhibitor used in CML treatment. We used MTT assay to measure cell viability and Hoechst/PI assay to measure cell death. Results: Our findings reveal that BHB concentrations ranging from 1 mM to 5 mM, which fall within the physiological range of ketosis, elicit a minimal yet concentration-dependent reduction in cell viability. We also observed that while a 24-hour pre-treatment with BHB did not enhance the response of K562 cells to ponatinib, prolonged ketosis (4 days) improved response of cells to the drug by decreasing final cell viability from 25.15% to 13.12%. The primary mode of viability inhibition by ponatinib was cell death which was further intensified by exposure to prolonged ketosis. Conclusion: Ketosis induced by ketogenic diet of ketone body supplementation is considered as safe and effective adjuvant cancer therapy options and here, we report its potential effectiveness in the context of CML.
dc.identifier.citationÖzkaya, A. B., Malcanlı, S., & Gönül Geyik, Ö. (2025). Prolonged Β-Hydroxybutyrate-Mediated Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells. Journal of Basic and Clinical Health Sciences, 9(1), 239-244. https://doi.org/10.30621/jbachs.1612561
dc.identifier.doi10.30621/jbachs.1612561
dc.identifier.endpage244
dc.identifier.issue1
dc.identifier.startpage239
dc.identifier.urihttps://doi.org/10.30621/jbachs.1612561
dc.identifier.urihttps://dergipark.org.tr/en/pub/jbachs/issue/90268/1612561
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6175
dc.identifier.volume9
dc.institutionauthorGeyik, Öykü Gönül
dc.institutionauthoridÖykü Gönül Geyik / 0000-0003-3014-1253
dc.institutionauthoridSenanur Malcanlı / 0000-0003-3811-8146
dc.language.isoen
dc.publisherDokuz Eylul University
dc.relation.ispartofJournal Of Basic And Clinical Health Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectketosis
dc.subjectβ-hydroxybutyrate
dc.subjectcancer
dc.subjectchronic myeloid leukaemia
dc.subjectketogenic diet
dc.titleProlonged Β-Hydroxybutyrate-Mediated Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells
dc.typeArticle

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