The activity of xenobiotic enzymes and the cytotoxicity of mitoxantrone in MCF 7 human breast cancer cells treated with inducing agents

Chemico-biological Interactions
S J LiM H Grant

Abstract

This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these, BA was the most effective, increasing cytochrome P450 dependent metabolism 64-fold and DT-diaphorase activity 1.6-fold. R did not cause an increase in any of the enzyme activities measured and, in fact inhibited glutathione peroxidase activity. PB and DEX increased NADPH cytochrome c reductase activity but had no effect on either DT-diaphorase or cytochrome P450 dependent activities. BA potentiated the cytotoxicity of mitoxantrone in terms of leakage of lactate dehydrogenase (LDH) activity and loss of reduced glutathione (GSH) and protein from cultures. PB had a smaller potentiating effect on cytotoxicity and DEX had no effect. Studies with the enzyme inhibitors, dicoumarol (inhibits DT-diaphorase) and metyrapone (inhibits cytochrome P450), indicate that at least two reactive species are involved in mitoxantrone cytotoxicity. One intermediate, formed by cytochrome P450, caused LDH leakage and GSH depletion. Format...Continue Reading

References

Dec 1, 1978·In Vitro·D C AnuforoR V Smith
Jan 22, 1992·Biochemical Pharmacology·A R GoeptarN P Vermeulen
Apr 15, 1992·Biochemical Pharmacology·R J Riley, P Workman
Jan 1, 1991·Chemico-biological Interactions·P J O'Brien
Sep 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R M VromansN P Vermeulen
Jan 1, 1990·Pharmacology & Therapeutics·M Barry, J Feely
Mar 15, 1990·International Journal of Cancer. Journal International Du Cancer·J J Schlager, G Powis
Apr 15, 1989·Biochemical Pharmacology·S J Duthie, M H Grant
Feb 15, 1989·Archives of Biochemistry and Biophysics·J M MathisE R Simpson
Jan 1, 1985·Methods in Enzymology·I Carlberg, B Mannervik
Apr 29, 1986·Biochemical and Biophysical Research Communications·M D CrespiA Baldi
Apr 1, 1987·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F A ShepherdK I Pritchard
Oct 15, 1988·Biochemical Pharmacology·K A al-Gailany, A H Alwan
Jul 1, 1986·Annals of Internal Medicine·T D Shenkenberg, D D Von Hoff
Dec 1, 1983·Cancer Treatment Reviews·F E DurrR V Citarella
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·P L ChesisB N Ames
Aug 23, 1983·Biochimica Et Biophysica Acta·F CarmagnolH Jerome
Mar 1, 1994·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K MewesK P Zeller

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Citations

Apr 3, 2013·Archives of Toxicology·Luciana Grazziotin RossatoFernando Remião
Sep 21, 2013·Cardiovascular Toxicology·Luciana Grazziotin RossatoFernando Remião
Nov 8, 1996·Biochemical Pharmacology·D SchrenkS S Thorgeirsson
Jun 28, 2016·Archives of Toxicology·Roberto Marques DamianiJenifer Saffi
Feb 24, 2012·Pharmacological Reports : PR·Augustinus BaderSanja Pavlica

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