Dose-dependent protective and inductive effects of xanthohumol on oxidative DNA damage in Saccharomyces cerevisiae

Abstract

The effect of xanthohumol, a prenylflavonoid isolated from the hop plant (Humulus lupulus L.), on Saccharomyces cerevisiae DNA oxidative damage and viability was evaluated. Yeast cultures under oxidative stress, induced by H2O2, displayed stronger growth in the presence of 5 mg/L of xanthohumol than cultures with only H2O2. Likewise, DNA damage assessed by the comet assay was significantly lower in cells co-incubated with xanthohu- mol and H2O2. Accordingly, fluorescence of dichlorofluorescein in cells treated with H2O2 and xanthohumol was considerably lower than in cells exclusively treated with H2O2, in- dicative of a reactive oxygen species scavenging mechanism and consequent formation of oxidation products, as detected by mass spectrometry. However, at concentrations above 5 mg/L, xanthohumol elicited an opposite effect, leading to a slower growth rate and signifi- cant increase in DNA damage. A yeast yap1 deletion mutant strain sensitive to oxidative stress grew more slowly in the presence of at least 5 mg/L of xanthohumol than cultures of the wild type, suggesting that xanthohumol toxicity is mediated by oxidative stress. This evidence provides further insight into the impact of xanthohumol on yeast cells, support- ing dose-dependent antioxidant/antigenotoxic and prooxidant/genotoxic effects.