The antioxidant, rather than prooxidant, activities of quercetin on normal cells: Quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis

The bioflavonoid quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. Although the activity of quercetin is believed to be due to its antioxidative properties, it has recently been suggested that quercetin also has prooxidant activities, which might effect cytotoxicity directly. In this study, we used mouse thymocytes to investigate whether quercetin behaved as a protector against oxidative stress or as a cytotoxic agent. Quercetin treatment did not induce oxidative damage, but protected mouse thymocytes from glucose oxidase (GO)-mediated apoptosis in a dose-dependent manner. Furthermore, electrophoretic mobility shift assays revealed that quercetin (50 μM) treatment suppressed the GO-mediated DNA binding activity of redox state-sensitive transcription factors, such as NF-κB, AP-1, and p53. This result suggests that quercetin has antioxidative effects on thymocytes. More interestingly, quercetin treatment alone (50 μM) increased the DNA-binding activity of AP-1, which consisted of heterodimer of c-Jun and Fra-2. Finally, the antioxidant activity of quercetin was confirmed using a cell-free system of radical generation. Our findings suggest that quercetin protects mouse thymocytes from oxidative stress-mediated apoptosis and modulates the intracellular redox state through its antioxidant activity.