Xanthohumol is the major prenylated
flavonoid present in the hop plant Humulus lupulus L. (Cannabinaceae) and a common ingredient of beer. Recently,
xanthohumol has gained considerable interest due to its potential
cancer chemo-preventive effect. The aim of this study was to reveal the possible anti-genotoxic activity of
xanthohumol in metabolically competent human
hepatoma HepG2 cells, by use of the comet assay.
Xanthohumol by itself was neither cytotoxic nor genotoxic to the cells at concentrations below 10microM. However, a significant protective effect against the pro-
carcinogens benzo(a)pyrene (BaP) and 2-amino-3-methylimidazo[4,5-f]
quinoline (IQ) was observed at concentrations as low as 0.01microM. In cells treated with
xanthohumol in combination with
tert-butyl hydroperoxide (t-BOOH) - an inducer of
reactive oxygen species (ROS) - no protective effect was observed and
xanthohumol also showed no significant scavenging activity against
1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. On the other hand, HepG2 cells pre-treated with
xanthohumol showed significantly reduced levels of t-BOOH-induced
DNA strand breaks, indicating that its protective effect is mediated by induction of cellular defence mechanisms against oxidative stress. As
xanthohumol is known to be an effective inhibitor of
cytochrome P450 enzymes and an inducer of
NAD(P)H:
quinone reductase (QR), our findings can be explained by an inhibition of metabolic activation of pro-
carcinogens and/or by induction of
carcinogen-detoxifying and anti-oxidative
enzymes by
xanthohumol. These results provide evidence that
xanthohumol displays anti-genotoxic activity in metabolically competent human cells.