Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F17%3A00489413" target="_blank" >RIV/61388971:_____/17:00489413 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/17:10366553 RIV/86652036:_____/17:00489413
Result on the web
<a href="http://dx.doi.org/10.18632/oncotarget.21663" target="_blank" >http://dx.doi.org/10.18632/oncotarget.21663</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/oncotarget.21663" target="_blank" >10.18632/oncotarget.21663</a>
Alternative languages
Result language
angličtina
Original language name
Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
OncoTarget
ISSN
1949-2553
e-ISSN
—
Volume of the periodical
8
Issue of the periodical within the volume
61
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
103137-103153
UT code for WoS article
000419562500035
EID of the result in the Scopus database
2-s2.0-85035358010