The Anticancer Drug Ellipticine Activated with Cytochrome P450 Mediates DNA Damage Determining Its Pharmacological Efficiencies: Studies with Rats, Hepatic Cytochrome P450 Reductase Null (HRN (TM)) Mice and Pure Enzymes

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F15%3A10311951" target="_blank" >RIV/00216208:11310/15:10311951 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.3390/ijms16010284" target="_blank" >http://dx.doi.org/10.3390/ijms16010284</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms16010284" target="_blank" >10.3390/ijms16010284</a>

Result language
angličtina
Original language name
The Anticancer Drug Ellipticine Activated with Cytochrome P450 Mediates DNA Damage Determining Its Pharmacological Efficiencies: Studies with Rats, Hepatic Cytochrome P450 Reductase Null (HRN (TM)) Mice and Pure Enzymes
Original language description
Ellipticine is a DNA-damaging agent acting as a prodrug whose pharmacological efficiencies and genotoxic side effects are dictated by activation with cytochrome P450 (CYP). Over the last decade we have gained extensive experience in using pure enzymes and various animal models that helped to identify CYPs metabolizing ellipticine. In this review we focus on comparison between the in vitro and in vivo studies and show a necessity of both approaches to obtain valid information on CYP enzymes contributingto ellipticine metabolism. Discrepancies were found between the CYP enzymes activating ellipticine to 13-hydroxy-and 12-hydroxyellipticine generating covalent DNA adducts and those detoxifying this drug to 9-hydroxy-and 7-hydroellipticine in vitro and invivo. In vivo, formation of ellipticine-DNA adducts is dependent not only on expression levels of CYP3A, catalyzing ellipticine activation in vitro, but also on those of CYP1A that oxidize ellipticine in vitro mainly to the detoxificatio
Czech name
—
Czech description
—

Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
—

Project
<a href="/en/project/GA14-18344S" target="_blank" >GA14-18344S: Development of nanoparticle-based cytostatics and enzymes for enhanced chemotherapy of human neuroblastomas and study of mechanisms of their action</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Similar results(10)