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Institute of Organic Chemistry & Biochemistry, Collection of Czechoslovak Chemical Communications, 10(72), p. 1350-1364

DOI: 10.1135/cccc20071350



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The Anticancer Drug Ellipticine is an Inducer of Rat NAD(P)H:Quinone Oxidoreductase

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This paper is available in a repository.

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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.