Publication detail

The Anticancer Drug Ellipticine Induces Cytochromes P450 1A1, 1A2 and 3A, Cytochrome b(5) and NADPH:Cytochrome P450 Oxidoreductase in Rat Liver, Kidney and Lung

VRÁNOVÁ, I. MOSEROVÁ, M. HODEK, P. KIZEK, R. FREI, E. STIBOROVÁ, M.

Original Title

The Anticancer Drug Ellipticine Induces Cytochromes P450 1A1, 1A2 and 3A, Cytochrome b(5) and NADPH:Cytochrome P450 Oxidoreductase in Rat Liver, Kidney and Lung

Type

journal article in Web of Science

Language

English

Original Abstract

The antineoplastic alkaloid ellipticine is a prodrug, the pharmacological efficiency of which is dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation in target tissues. Using the Western blotting, we found that this compound increases protein expression of cytochrome b(5), CYP1A1, 1A2, 3A and NADPH: CYP oxidoreductase (POR) in livers, lungs and kidneys of rats treated (i.p.) with ellipticine. The ellipticine-mediated induction of these enzymes resulted in an increase in their enzymatic activities and ellipticine oxidation to 7-hydroxy-, 9-hydroxy-, 12-hydroxy-and 13-hydroxyellipticine, the metabolites that are both detoxication products (7-hydroxy-, 9-hydroxyellipticine) and metabolites responsible for generation ellipticine-derived DNA adducts (12-hydroxy- and 13-hydroxyellipticine). The results demonstrate that by inducing CYP1A1/2, 3A, POR and cytochrome b(5), ellipticine increases its own metabolism in rats, thereby modulating its own pharmacological and/or genotoxic potential.

Keywords

Ellipticine; Cytochromes P450; Protein Expression; Western Blotting; Metabolism

Authors

VRÁNOVÁ, I.; MOSEROVÁ, M.; HODEK, P.; KIZEK, R.; FREI, E.; STIBOROVÁ, M.

Released

1. 2. 2013

ISBN

1452-3981

Periodical

INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE

Year of study

8

Number

2

State

Republic of Serbia

Pages from

1586

Pages to

1597

Pages count

12

BibTex

@article{BUT145264,
  author="VRÁNOVÁ, I. and MOSEROVÁ, M. and HODEK, P. and KIZEK, R. and FREI, E. and STIBOROVÁ, M.",
  title="The Anticancer Drug Ellipticine Induces Cytochromes P450 1A1, 1A2 and 3A, Cytochrome b(5) and NADPH:Cytochrome P450 Oxidoreductase in Rat Liver, Kidney and Lung",
  journal="INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE",
  year="2013",
  volume="8",
  number="2",
  pages="1586--1597",
  issn="1452-3981"
}