Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells(325 views visite) De Rosa V, Monti M, Terlizzi C, Fonti R, Del Vecchio S, Iommelli F
Int J Mol Sc (ISSN: 1422-0067linking, 1661-6596, 1422-0067electronic), 2019 Jun 27; 20(13): N/D-N/D.
Keywords Parole chiave: Bcr-Abl, Oxphos, Aerobic Glycolysis, Chronic Myeloid Leukemia,
Affiliations Affiliazioni: *** IBB - CNR ***
Institute of Biostructures and Bioimaging, National Research Council, 80145 Naples, Italy., Department of Advanced Biomedical Sciences, University of Naples "Federico II", 80131 Naples, Italy., Department of Advanced Biomedical Sciences, University of Naples "Federico II", 80131 Naples, Italy. delvecc@unina.it.,
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Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells
Since many oncogenes, including BCR-ABL, may promote the acquisition and maintenance of the glycolytic phenotype, we tested whether treatment of BCR-ABL-driven human leukemia cells with imatinib, a selective BCR-ABL inhibitor, can modulate the expression of key glycolytic enzymes and mitochondrial complex subunits thus causing alterations of glucose metabolism. BCR-ABL-driven K562 and KCL-22 cells were incubated with increasing concentrations of imatinib to preliminarily test drug sensitivity. Then untreated and treated cells were analyzed for levels of BCR-ABL signaling mediators and key proteins of glycolytic cascade and oxidative phosphorylation. Effective inhibition of BCR-ABL caused a concomitant reduction of p-ERK1/2, p-AKT, phosphorylated form of STAT3 (at Tyr705 and Ser727), c-Myc and cyclin D1 along with an increase of cleaved PARP and caspase 3 at 48 h after treatment. Furthermore, a strong reduction of the hexokinase II (HKII), phosphorylated form of PKM2 (at Tyr105 and Ser37) and lactate dehydrogenase A (LDH-A) was observed in response to imatinib along with a strong upregulation of mitochondrial complexes (OXPHOS). According to these findings, a significant reduction of glucose consumption and lactate secretion along with an increase of intracellular ATP levels was observed in response to imatinib. Our findings indicate that imatinib treatment of BCR-ABL-driven human leukemia cells reactivates mitochondrial oxidative phosphorylation thus allowing potential co-targeting of BCR-ABL and OXPHOS.
Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells
3 Records (1 escludendo Abstract e Conferenze). Impact factor totale: 15.17 (8.738 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 15.169 (8.751 escludendo Abstract e Conferenze).
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