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Halama, A.* ; Kulinski, M.* ; Dib, S.S.* ; Zaghlool, S.B.* ; Siveen, K.S.* ; Iskandarani, A.* ; Zierer, J.* ; Prabhu, K.S.* ; Satheesh, N.J.* ; Bhagwat, A.M.* ; Uddin, S.* ; Kastenmüller, G. ; Elemento, O.* ; Gross, S.S.* ; Suhre, K.*

Accelerated lipid catabolism and autophagy are cancer survival mechanisms under inhibited glutaminolysis.

Cancer Lett. 430, 133-147 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy. Simultaneously inhibiting glutaminolysis and either beta oxidation with trimetazidine or autophagy with chloroquine both induced cancer cell death. Here we identified metabolic escape mechanisms contributing to cancer cell survival under treatment and we suggest potentially translational strategy for combined cancer therapy, given that chloroquine is an FDA approved drug. Our findings are first to show efficiency of combined inhibition of glutaminolysis and beta oxidation as potential anti-cancer strategy as well as add to the evidence that combined inhibition of glutaminolysis and autophagy may be effective in glutamine-addicted cancers.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cancer Metabolism ; Glutaminolysis Inhibition ; Cancer Survival Mechanisms ; Beta-oxidation ; Autophagy; Polycyclic Aromatic-hydrocarbons; Lung Epithelial-cells; Yangtze-river Delta; 6 European Cities; Ambient Air; Oxidative Stress; Mouse Lung; A549 Cells; Cytotoxic Responses; Seasonal-variation
Sprache
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0304-3835
e-ISSN 0304-3835
Zeitschrift Cancer Letters
Quellenangaben Band: 430, Heft: , Seiten: 133-147 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Po Box 211, 1000 Ae Amsterdam, Netherlands
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Bioinformatics and Systems Biology (IBIS)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503700-001
DOI 10.1016/j.canlet.2018.05.017
WOS ID WOS:000436912200013
Scopus ID 85047436240
Scopus ID 85047436240&
PubMed ID 29777783
Erfassungsdatum 2018-06-26
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