Quercetin-induced PC12 cell death accompanied by caspase-mediated DNA fragmentation.
ABSTRACT 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 (H2O2) on cell death of PC12 cells, a neuronal cell line. We showed that quercetin at 10-30 microM alone caused cell death accompanied by caspase-mediated DNA fragmentation in undifferentiated PC12 cells. Quercetin did not inhibit and rather enhanced 0.1 mM H2O2-induced cell death. The toxic effect of quercetin was not inhibited by antioxidants such as N-acetylcysteine and GSH, although H2O2-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.
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ABSTRACT: Quercetin is a potent free radical–scavenging antioxidant exerting chemopreventive activity by reducing oxidative stresses. However, oxidized quercetin behaves as a prooxidant, which can lead to paradoxical effects. This study was conducted to investigate the effects of quercetin supplementation on 1,2-dimethylhydrazine (DMH)–induced oxidative DNA damage and precancerous lesion formation in the colon. Male Sprague-Dawley rats were randomized into 5 groups. The rats in groups 3, 4, and 5 were treated with DMH (30 mg/kg body weight IP), twice on weeks 2 and 3. The experimental diets were as follows: control diet (group 1), 2% quercetin diet (group 2), control diet (group 3), 0.2% quercetin diet (group 4), and 2% quercetin diet (group 5). The DMH-induced oxidative tissue damage was examined 24 hours after the first DMH injection, and the aberrant crypt foci formation was measured at week 12. The results show the following: (1) that DMH significantly increased the level of 8-hydroxyguanine (8-OH-Gua) in the liver, where the metabolic conversion of DMH occurs, but did not significantly change the level of 8-OH-Gua in the colon; (2) that both the 0.2% and 2% quercetin supplementation suppressed the extent of 8-OH-Gua formation in the liver; (3) that dietary quercetin did not affect the formation of aberrant crypt foci; and (4) that 2% quercetin supplementation only slightly increased the liver oxidative damage without statistical significance. These results indicate that quercetin may not be an effective anticarcinogen against DMH-induced colon cancer, where oxidative tissue damage is not a primary event in the formation of a precancerous region. The context of quercetin as a hepatoprotective agent, however, must be emphasized.Nutrition Research 10/2007; 27(10):659-664. · 2.59 Impact Factor
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