Cytochrome b(5) Increases Cytochrome P450 3A4-Mediated Activation of Anticancer Drug Ellipticine to 13-Hydroxyellipticine Whose Covalent Binding to DNA Is Elevated by Sulfotransferases and N,O-Acetyltransferases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F12%3A10125664" target="_blank" >RIV/00216208:11310/12:10125664 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62156489:43210/12:00198398 RIV/00216208:11130/12:8100 RIV/00064203:_____/12:8100

Výsledek na webu

<a href="http://dx.doi.org/10.1021/tx3000335" target="_blank" >http://dx.doi.org/10.1021/tx3000335</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/tx3000335" target="_blank" >10.1021/tx3000335</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cytochrome b(5) Increases Cytochrome P450 3A4-Mediated Activation of Anticancer Drug Ellipticine to 13-Hydroxyellipticine Whose Covalent Binding to DNA Is Elevated by Sulfotransferases and N,O-Acetyltransferases

Popis výsledku v původním jazyce

The antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological efficiency is dependent on its cytochrome P450 (P450)- and/or peroxidase-mediated activation in target tissues. The P450 3A4 enzyme oxidizes ellipticine to five metabolites, mainly to 13-hydroxy- and 12-hydroxyellipticine, the metabolites responsible for the formation of ellipticine-13-ylium and ellipticine-12-ylium ions that generate covalent DNA adducts. Cytochrome b(5) alters the ratio of ellipticine metabolites formed by P450 3A4. While the amounts of the detoxication metabolites (7-hydroxy- and 9-hydroxyellipticine) were not changed with added cytochrome b(5), 12-hydroxy- and 13-hydroxyellipticine, and ellipticine N-2-oxide increased considerably. The P450 3A4-mediated oxidation of ellipticine was significantly changed only by holo-cytochrome b(5), while apo-cytochrome b(5) without heme or Mn-cytochrome b(5) had no such effect. The change in amounts of metabolites resulted in an increased formation of cova

Název v anglickém jazyce

Cytochrome b(5) Increases Cytochrome P450 3A4-Mediated Activation of Anticancer Drug Ellipticine to 13-Hydroxyellipticine Whose Covalent Binding to DNA Is Elevated by Sulfotransferases and N,O-Acetyltransferases

Popis výsledku anglicky

The antineoplastic alkaloid ellipticine is a prodrug, whose pharmacological efficiency is dependent on its cytochrome P450 (P450)- and/or peroxidase-mediated activation in target tissues. The P450 3A4 enzyme oxidizes ellipticine to five metabolites, mainly to 13-hydroxy- and 12-hydroxyellipticine, the metabolites responsible for the formation of ellipticine-13-ylium and ellipticine-12-ylium ions that generate covalent DNA adducts. Cytochrome b(5) alters the ratio of ellipticine metabolites formed by P450 3A4. While the amounts of the detoxication metabolites (7-hydroxy- and 9-hydroxyellipticine) were not changed with added cytochrome b(5), 12-hydroxy- and 13-hydroxyellipticine, and ellipticine N-2-oxide increased considerably. The P450 3A4-mediated oxidation of ellipticine was significantly changed only by holo-cytochrome b(5), while apo-cytochrome b(5) without heme or Mn-cytochrome b(5) had no such effect. The change in amounts of metabolites resulted in an increased formation of cova

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

1075-1085

Kód UT WoS článku

000304235000011

EID výsledku v databázi Scopus

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