Carcinogenesis, Vol 19, 1583-1589, Copyright © 1998 by Oxford University Press
CA Musonda and JK Chipman
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.
ARTICLES
Quercetin inhibits hydrogen peroxide (H2O2)-induced NF-kappaB DNA binding activity and DNA damage in HepG2 cells
School of Biochemistry, The University of Birmingham, Edgbaston, UK.
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