Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F20%3A10417716" target="_blank" >RIV/00216208:11160/20:10417716 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=K6zy1jt4qq" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=K6zy1jt4qq</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cancers12113127" target="_blank" >10.3390/cancers12113127</a>
Alternative languages
Result language
angličtina
Original language name
Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3
Original language description
Olaparib is a potent poly (ADP-ribose) polymerase inhibitor currently used in targeted therapy for treating cancer cells with BRCA mutations. Here we investigate the possible interference of olaparib with daunorubicin (Daun) metabolism, mediated by carbonyl-reducing enzymes (CREs), which play a significant role in the resistance of cancer cells to anthracyclines. Incubation experiments with the most active recombinant CREs showed that olaparib is a potent inhibitor of the aldo-keto reductase 1C3 (AKR1C3) enzyme. Subsequent inhibitory assays in the AKR1C3-overexpressing cellular model transfected human colorectal carcinoma HCT116 cells, demonstrating that olaparib significantly inhibits AKR1C3 at the intracellular level. Consequently, molecular docking studies have supported these findings and identified the possible molecular background of the interaction. Drug combination experiments in HCT116, human liver carcinoma HepG2, and leukemic KG1 alpha cell lines showed that this observed interaction can be exploited for the synergistic enhancement of Daun's antiproliferative effect. Finally, we showed that olaparib had no significant effect on the mRNA expression of AKR1C3 in HepG2 and KG1 alpha cells. In conclusion, our data demonstrate that olaparib interferes with anthracycline metabolism, and suggest that this phenomenon might be utilized for combating anthracycline resistance.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancers
ISSN
2072-6694
e-ISSN
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Volume of the periodical
12
Issue of the periodical within the volume
11
Country of publishing house
CH - SWITZERLAND
Number of pages
16
Pages from-to
3127
UT code for WoS article
000592990800001
EID of the result in the Scopus database
2-s2.0-85095754066