Inhibition of human anthracycline reductases by emodin - A possible remedy for anthracycline resistance
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F16%3A10328283" target="_blank" >RIV/00216208:11160/16:10328283 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0041008X16300035" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0041008X16300035</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.taap.2016.01.003" target="_blank" >10.1016/j.taap.2016.01.003</a>
Alternative languages
Result language
angličtina
Original language name
Inhibition of human anthracycline reductases by emodin - A possible remedy for anthracycline resistance
Original language description
The clinical application of anthracyclines, like daunorubicin and doxorubicin, is limited by two factors: dose related cardiotoxicity and drug resistance. Both have been linked to reductive metabolism of the parent drug to their metabolites daunorubicinol and doxorubicinol, respectively. These metabolites show significantly less anti-neoplastic properties as their parent drugs and accumulate in cardiac tissue leading to chronic cardiotoxicity. Therefore, we aimed to identify novel and potent natural inhibitors for anthracycline reductases, which enhance the anticancer effect of anthracyclines by preventing the development of anthracycline resistance. Human enzymes responsible for the reductive metabolism of daunorubicin were tested for their sensitivity towards anthrachinones, in particular emodin and anthraflavic acid. Intense inhibition kinetic data for the most effective daunorubicin reductases, including IC50-and K-i-values, the mode of inhibition, as well as molecular docking, were compiled. Subsequently, a cytotoxicity profile and the ability of emodin to reverse daunorubicin resistance were determined using multiresistant A549 lung cancer and HepG2 liver cancer cells. Emodin potently inhibited the four main human daunorubicin reductases in vitro. Further, we could demonstrate that emodin is able to synergistically sensitize human cancer cells towards daunorubicin at clinically relevant concentrations. Therefore, emodin may yield the potential to enhance the therapeutic effectiveness of anthracyclines by preventing anthracycline resistance via inhibition of the anthracycline reductases. In symphony with its known pharmacological properties, emodin might be a compound of particular interest in the management of anthracycline chemotherapy efficacy and their adverse effects.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/EE2.3.30.0061" target="_blank" >EE2.3.30.0061: Increasing of the R&D capacity at Charles University through new positions for graduates of doctoral studies</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology and Applied Pharmacology
ISSN
0041-008X
e-ISSN
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Volume of the periodical
293
Issue of the periodical within the volume
February
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
21-29
UT code for WoS article
000370303700003
EID of the result in the Scopus database
2-s2.0-84954213393