Prolonged Β-Hydroxybutyrate-Mediated Ketosis Enhances Ponatinib Response of K562 Chronic Myeloid Leukaemia Cells
Küçük Resim Yok
Tarih
31 Ocak 2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Dokuz Eylul University
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Purpose: 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.
Açıklama
Anahtar Kelimeler
ketosis, β-hydroxybutyrate, cancer, chronic myeloid leukaemia, ketogenic diet
Kaynak
Journal Of Basic And Clinical Health Sciences
WoS Q Değeri
Scopus Q Değeri
Cilt
9
Sayı
1
Künye
Özkaya, 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
