Collect. Czech. Chem. Commun. 2007, 72, 1350-1364

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


The antineoplastic agent ellipticine was investigated for its ability to induce the biotransformation enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase, EC 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.