Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B

Vališ, Karel; Grobárová, Valeria; Hernychová, Lucie; Bugáňová, Martina; Kavan, Daniel; Kalous, M.; Černý, Jiří; Stodůlková, Eva; Kuzma, Marek; Flieger, Miroslav; Černý, J.; Novák, Petr

doi:https://dx.doi.org/10.18632/oncotarget.21663

Number of the records: 1

Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B

1.

SYSNO ASEP	0489413
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B
Author(s)	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, ORCID}
Source Title	OncoTarget. - : Impact Journals LLC - ISSN 1949-2553 Roč. 8, č. 61 (2017), s. 103137-103153
Number of pages	17 s.
Language	eng - English
Country	US - United States
Keywords	metabolism ; leukemia ; naphthoquinones
Subject RIV	EE - Microbiology, Virology
OECD category	Microbiology
Subject RIV - cooperation	Institute of Biotechnology - Microbiology, Virology
R&D Projects	GA13-16565S GA ČR - Czech Science Foundation (CSF)
	GP14-21095P GA ČR - Czech Science Foundation (CSF)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LO1509 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	MBU-M - RVO:61388971
UT WOS	000419562500035
EID SCOPUS	85035358010
DOI	10.18632/oncotarget.21663
Annotation	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.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2019

Number of the records: 1