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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 c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651622/ https://www.ncbi.nlm.nih.gov/pubmed/31252559 http://dx.doi.org/10.3390/ijms20133134 |
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author | De Rosa, Viviana Monti, Marcello Terlizzi, Cristina Fonti, Rosa Del Vecchio, Silvana Iommelli, Francesca |
author_facet | De Rosa, Viviana Monti, Marcello Terlizzi, Cristina Fonti, Rosa Del Vecchio, Silvana Iommelli, Francesca |
author_sort | De Rosa, Viviana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6651622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66516222019-08-08 Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells De Rosa, Viviana Monti, Marcello Terlizzi, Cristina Fonti, Rosa Del Vecchio, Silvana Iommelli, Francesca Int J Mol Sci Communication 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. MDPI 2019-06-27 /pmc/articles/PMC6651622/ /pubmed/31252559 http://dx.doi.org/10.3390/ijms20133134 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication De Rosa, Viviana Monti, Marcello Terlizzi, Cristina Fonti, Rosa Del Vecchio, Silvana Iommelli, Francesca Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title | Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title_full | Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title_fullStr | Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title_full_unstemmed | Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title_short | Coordinate Modulation of Glycolytic Enzymes and OXPHOS by Imatinib in BCR-ABL Driven Chronic Myelogenous Leukemia Cells |
title_sort | coordinate modulation of glycolytic enzymes and oxphos by imatinib in bcr-abl driven chronic myelogenous leukemia cells |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651622/ https://www.ncbi.nlm.nih.gov/pubmed/31252559 http://dx.doi.org/10.3390/ijms20133134 |
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