Quercetin inhibits hydrogen peroxide (H2O2)-induced NF-kappaB DNA binding activity and DNA damage in HepG2 cells

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Abstract
We have investigated the effect of the plant-derived flavonoid quercetin in relation to potential oxidant and antioxidant activity on nuclear factor kappaB (NF-kappaB) binding activity and DNA integrity in HepG2 cells. Gel mobility shift assays using a gamma-32P-labelled NF-kappaB oligonucleotide probe showed that treatment of HepG2 cells with quercetin (up to 10 microM, sub-cytotoxic) did not elevate NF-kappaB binding activity of nuclear extract protein but did inhibit binding activity of an extract from cells treated with the oxidant H2O2. A similar inhibition by quercetin of H2O2-induced NF-kappaB transcriptional activation was demonstrated using a cat reporter gene assay. Considering oxidative DNA damage, using single cell gel electrophoresis (comet) assay we have demonstrated that quercetin (10 microM and below) did not induce DNA strand breaks. However, a marked and statistically significant (P < 0.01 at 10 microM) inhibition of strand breakage produced by H2O2 was detected. The specific formation of 8-oxo-2'-deoxyguanosine (8-oxodG) in calf thymus DNA exposed to either gamma-irradiation or the Fenton reaction system was also inhibited (P < 0.01 at 10 microM) by quercetin in a dose-dependent manner. This was not accompanied by formation of 8-oxodG by quercetin itself. The inhibition of 8-oxodG formation by gamma-irradiation was more potent (IC50 = 0.05 microM) than that by the Fenton reaction (IC50 = 0.5 microM), implying that the mechanism of protection may be different between the two systems. The inhibition of both NF-kappaB binding activity and oxidative DNA damage suggests that its antioxidant potential outweighs its oxidative potential in a cellular environment, which may contribute to anticarcinogenic and anti-inflammatory effects.

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