Collect. Czech. Chem. Commun.
2007, 72, 1350-1364
https://doi.org/10.1135/cccc20071350
The Anticancer Drug Ellipticine is an Inducer of Rat NAD(P)H:Quinone Oxidoreductase
Marie Stiborováa,*, Helena Dračínskáa, Dagmar Aimováa, Petr Hodeka, Jiří Hudečeka, Helena Ryšlaváa, Heinz H. Schmeiserb and Eva Freib
a Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
b Division of Molecular Toxicology, German Cancer Research Center, In Neuenheimer Feld 280, 69120 Heidelberg, Germany
Abstract
The antineoplastic agent ellipticine was investigated for its ability to induce the biotransformation enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase, EC 1.6.99.2) in male Wistar rats. Using the real-time polymerase chain reaction, the levels of NAD(P)H:quinone oxidoreductase mRNA were determined in livers, kidneys and lungs of rats treated intraperitoneally with ellipticine (40 mg/kg body weight) and of control (untreated) rats. Cytosolic fractions were isolated from the same tissues of control and ellipticine-treated rats and tested for NAD(P)H:quinone oxidoreductase protein expression and its enzymatic activity. The results demonstrate that ellipticine is a potent inducer of NAD(P)H:quinone oxidoreductase in rat livers and kidneys, while no induction of this enzyme was detectable in rat lungs. The increase in levels of NAD(P)H:quinone oxidoreductase mRNA correlates with the increase in expression of its protein and enzymatic activity, measured with menadione and 3-nitrobenzanthrone as substrates. The results, the identification of the potential of ellipticine to induce NAD(P)H:quinone oxidoreductase, suggest that this drug is capable of modulating biological efficiencies of the toxicants and/or drugs that are reductively metabolized by this enzyme.
Keywords: NAD(P)H:quinone oxidoreductase; Enzyme induction; Anticancer drugs; Carcinogens; Metabolic activation; Ellipticine.
References: 61 live references.
