Počet záznamů: 1
Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B
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SYSNO ASEP 0489413 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B Tvůrce(i) Vališ, Karel (MBU-M) ORCID
Grobárová, Valeria (MBU-M)
Hernychová, Lucie (MBU-M)
Bugáňová, Martina (MBU-M)
Kavan, Daniel (MBU-M) RID, ORCID
Kalous, M. (CZ)
Černý, Jiří (BTO-N) RID, ORCID
Stodůlková, Eva (MBU-M) ORCID
Kuzma, Marek (MBU-M) ORCID, RID
Flieger, Miroslav (MBU-M) ORCID
Černý, J. (CZ)
Novák, Petr (MBU-M) RID, ORCIDZdroj.dok. OncoTarget. - : Impact Journals LLC - ISSN 1949-2553
Roč. 8, č. 61 (2017), s. 103137-103153Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova metabolism ; leukemia ; naphthoquinones Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology Vědní obor RIV – spolupráce Biotechnologický ústav - Mikrobiologie, virologie CEP GA13-16565S GA ČR - Grantová agentura ČR GP14-21095P GA ČR - Grantová agentura ČR ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LO1509 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora MBU-M - RVO:61388971 UT WOS 000419562500035 EID SCOPUS 85035358010 DOI 10.18632/oncotarget.21663 Anotace Abnormalities in cancer metabolism represent potential targets for cancer therapy. We have recently identified a natural compound Quambalarine B (QB), which inhibits proliferation of several leukemic cell lines followed by cell death. We have predicted ubiquinone binding sites of mitochondrial respiratory complexes as potential molecular targets of QB in leukemia cells. Hence, we tracked the effect of QB on leukemia metabolism by applying several omics and biochemical techniques. We have confirmed the inhibition of respiratory complexes by QB and found an increase in the intracellular AMP levels together with respiratory substrates. Inhibition of mitochondrial respiration by QB triggered reprogramming of leukemic cell metabolism involving disproportions in glycolytic flux, inhibition of proteins O-glycosylation, stimulation of glycine synthesis pathway, and pyruvate kinase activity, followed by an increase in pyruvate and a decrease in lactate levels. Inhibition of mitochondrial complex I by QB suppressed folate metabolism as determined by a decrease in formate production. We have also observed an increase in cellular levels of several amino acids except for aspartate, indicating the dependence of Jurkat (T-ALL) cells on aspartate synthesis. These results indicate blockade of mitochondrial complex I and II activity by QB and reduction in aspartate and folate metabolism as therapeutic targets in T-ALL cells. Anti-cancer activity of QB was also confirmed during in vivo studies, suggesting the therapeutic potential of this natural compound. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2019
Počet záznamů: 1