Meta-Biol

• Pathways

Quinone reductases 1 and 2 (NQO1 and NQO2) comprise the mammalian quinone reductase family of enzymes responsible for performing FAD-mediated reductions of quinone substrates. In contrast to NQO1, which uses NADPH as a co-substrate, NQO2 uses a rare group of hydride donors, N-methyl or N-ribosyl nicotinamide (RFDHN). NQO2 is active in dimeric form, binding one FAD group per subunit (Wu et al. 1997). NQO2 can transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage (Celli et al. 2006, Knox et al. 2000).

Melatonin (MLT) has antioxidant effects and is able to bind NQO2, inhibiting its activity. Inhibition of NQO2 may lead to protection of cells against the production of highly reactive species (Calamini et al. 2008). Resveratrol is a phyto-polyphenol that is present in grapes and in significant amounts in grape juice and wines, particularly red wine. Resveratrol was found to be an anti-oxidant and a cancer chemopreventive agent (Jang et al. 1997). Its presence in red wine was also suggested to have cardioprotective effects, the so-called “French paradox”; an observation of lower incidence of cardiovascular disease in some French regions where red wine and saturated fats are consumed in greater quantities than in the US (Renaud & de Lorgeril 1992, Bradamante et al. 2004). The highest affinity target of resveratrol is NQO2. By inhibiting NQO2, resveratrol may protect cells against reactive intermediates and eventually cancer (Buryanovskyy et al. 2004, St John et al. 2013).