Translational Therapeutics

British Journal of Cancer (2006) 95, 1229–1233. doi:10.1038/sj.bjc.6603414 www.bjcancer.com
Published online 10 October 2006

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

D Jamieson1, A T Y Tung1, R J Knox2 and A V Boddy1

  1. 1Northern Institute for Cancer Research, University of Newcastle upon Tyne, Paul O'Gorman Building, Medical School, Newcastle upon Tyne NE2 4HH, UK
  2. 2Protherics plc., Building 115, Porton Down Science Park, Salisbury, Wiltshire SP4 0JQ, UK

Correspondence: Dr D Jamieson, E-mail: david.jamieson@newcastle.ac.uk

Received 31 July 2006; Revised 31 August 2006; Accepted 7 September 2006; Published online 10 October 2006.

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Abstract

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species.

Keywords:

mitomycin C, NQO1, NQO2, bioreductive drugs