Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation(Pharmacology)

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Flavonoids have been reported to be potent antioxidants and beneficial in oxidative stress related diseases. Quercetin, a major flavonoid in food, deserves much attention because of its antioxidative activity. However, the actions of flavonoids including quercetin are complex and paradoxical. Quercetin caused apoptosis and/or cell death in various cells including cancer cells and normal cells. In this study, we investigated the effects of quercetin with or without hydrogen peroxide (H_2O_2) on cell death of PC12 cells, a neuronal cell line. We showed that quercetin at 10-30μM alone caused cell death accompanied by caspase-mediated DNA fragmentation in undifferentiated PC12 cells. Quercetin did not inhibit and rather enhanced 0.1 HIM H_2O_2-induced cell death. The toxic effect of quercetin was not inhibited by antioxidants such as N-acetylcysteine and GSH, although H_2O_2-induced cell death was inhibited by the antioxidants. Quercetin-induced cell death was reduced by 2 h treatment with nerve growth factor and serum. In addition, quercetin caused cell death in differentiated PC12 cells that were cultured with nerve growth factor for 6 d. Genistein, a soy isoflavone that has the pro-apoptotic activity, also caused cell death with DNA fragmentation. Further evaluation of the potential of dietary flavonoids as neuroprotective reagents is needed.
公益社団法人日本薬学会の論文
2007-04-01