Dose-Dependent Protective and Inductive Effects of Xanthohumol on Oxidative DNA Damage in Saccharomyces cerevisiae

Daniel O. Carvalho¹, Rui Oliveira², Björn Johansson³ and Luís F. Guido^1*

¹REQUIMTE/LAQV – Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre 687, PT-4169-007 Porto, Portugal
²Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Department of Biology, University of Minho, Campus de Gualtar, PT-4710-057 Braga, Portugal
³Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus de Gualtar, PT-4710-057 Braga, Portugal

Article history:
Received May 13, 2015
Accepted October 27, 2015

Key words:
genotoxic and antigenotoxic effects, antioxidant and prooxidant capacity, comet assay, Saccharomyces cerevisiae, xanthohumol, yeast viability

Summary:

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 xanthohumol and H2O2. Accordingly, fluorescence of dichlorofluorescein in cells treated with H₂O₂ and xanthohumol was considerably lower than in cells exclusively treated with H₂O₂, indicative 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 significant 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, supporting dose-dependent antioxidant/antigenotoxic and prooxidant/genotoxic effects.

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