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  Imatinib (STI571)-Mediated Changes in Glucose Metabolism in Human Leukemia BCR-ABL-Positive Cells

Gottschalk, S., Anderson, N., Hainz, C., Eckhardt, S., & Serkova, N. (2004). Imatinib (STI571)-Mediated Changes in Glucose Metabolism in Human Leukemia BCR-ABL-Positive Cells. Clinical Cancer Research, 10(19), 6661-6668. doi:10.1158/1078-0432.CCR-04-0039.

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Gottschalk, S1, Author              
Anderson , N, Author
Hainz, C, Author
Eckhardt, SG, Author
Serkova, NJ, Author
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1External Organizations, ou_persistent22              

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 Abstract: The therapeutic efficacy of imatinib mesylate (Gleevec) is based on its specific inhibition of the BCR-ABL oncogene protein, a widely expressed tyrosine kinase in chronic myelogenous leukemia (CML) cells. The goal of this study was to evaluate glucose metabolism in BCR-ABL-positive cells that are sensitive to imatinib exposure. Two human BCR-ABL-positive cell lines (CML-T1 and K562) and one BCR-ABL-negative cell line (HC-1) were incubated with different imatinib concentrations for 96 hours. Magnetic resonance spectroscopy on cell acid extracts was performed to evaluate [1-13C]glucose metabolism, energy state, and changes in endogenous metabolites after incubation with imatinib. Imatinib induced a concentration-dependent inhibition of cell proliferation in CML-T1 (IC50, 0.69 ± 0.06 μmol/L) and K562 cells (IC50, 0.47 ± 0.04 μmol/L), but not in HC-1 cells. There were no metabolic changes in imatinib-treated HC-1 cells. In BCR-ABL-positive cells, the relevant therapeutic concentrations of imatinib (0.1–1.0 μmol/L) decreased glucose uptake from the media by suppressing glycolitic cell activity (C3-lactate at 0.25 mmol/L, 65 for K562 and 77 for CML-T1 versus control). Additionally, the activity of the mitochondrial Krebs cycle was increased (C4-glutamate at 0.25 μmol/L, 147 for K562 and 170 for CML-T1). The improvement in mitochondrial glucose metabolism resulted in an increased energy state (nucleoside triphosphate/nucleoside diphosphate at 0.25 μmol/L, 130 for K562 and 125 for CML-T1). Apoptosis was observed at higher concentrations. Unlike standard chemotherapeutics, imatinib, without cytocidal activity, reverses the Warburg effect in BCR-ABL-positive cells by switching from glycolysis to mitochondrial glucose metabolism, resulting in decreased glucose uptake and higher energy state.

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 Dates: 2004-10
 Publication Status: Published in print
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 Identifiers: DOI: 10.1158/1078-0432.CCR-04-0039
BibTex Citekey: GottschalkAHES2004
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Title: Clinical Cancer Research
  Other : Clin. Cancer Res.
Source Genre: Journal
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Publ. Info: Denville, NJ : Association for Cancer Research
Pages: - Volume / Issue: 10 (19) Sequence Number: - Start / End Page: 6661 - 6668 Identifier: ISSN: 1078-0432
CoNE: https://pure.mpg.de/cone/journals/resource/954925605818