Perturbation of energy metabolism by fatty-acid derivative AIC-47 and imatinib in BCR-ABL-harboring leukemic cells

Highlights • Imatinib strongly suppresses Warburg effect through the down-regulation of PTBP1. • Fatty-acid oxidation (FAO) supports glucose-independent survival in imatinib-treated cells. • Inactivation of BCR-ABL activates compensatory FAO. • AIC-47 perturbs both glycolysis and FAO. • The inhibiti...

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Veröffentlicht in:	Cancer letters 2016-02, Vol.371 (1), p.1-11
Hauptverfasser:	Shinohara, Haruka, Kumazaki, Minami, Minami, Yosuke, Ito, Yuko, Sugito, Nobuhiko, Kuranaga, Yuki, Taniguchi, Kohei, Yamada, Nami, Otsuki, Yoshinori, Naoe, Tomoki, Akao, Yukihiro
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Antigens, CD34 - metabolism Antineoplastic Combined Chemotherapy Protocols - pharmacology BCR-ABL Binding sites Cancer Conflicts of interest CPT1C Dose-Response Relationship, Drug Drug Synergism Energy Metabolism - drug effects Enzymes Experiments Fatty Acids - pharmacology Fatty-acid oxidation Fusion Proteins, bcr-abl - genetics Fusion Proteins, bcr-abl - metabolism Glycolysis - drug effects Hematology, Oncology and Palliative Medicine Heterocyclic Compounds, 1-Ring - pharmacology Heterogeneous-Nuclear Ribonucleoproteins - genetics Heterogeneous-Nuclear Ribonucleoproteins - metabolism Humans Imatinib Imatinib Mesylate - pharmacology Immunoglobulins K562 Cells Ketones - pharmacology Kinases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Metabolism MicroRNAs - genetics MicroRNAs - metabolism Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Oxidation-Reduction Polypyrimidine Tract-Binding Protein - genetics Polypyrimidine Tract-Binding Protein - metabolism Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism Protein Kinase Inhibitors - pharmacology Proteins Pyruvate Kinase - genetics Pyruvate Kinase - metabolism RNA Interference Stem cells Transfection Warburg effect
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Zusammenfassung:	Highlights • Imatinib strongly suppresses Warburg effect through the down-regulation of PTBP1. • Fatty-acid oxidation (FAO) supports glucose-independent survival in imatinib-treated cells. • Inactivation of BCR-ABL activates compensatory FAO. • AIC-47 perturbs both glycolysis and FAO. • The inhibition of glycolysis and FAO can be effective for the CD34+ fraction.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2015.11.020