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

Daniel O Carvalho,Luís F Guido,Björn Johansson,Rui Oliveira

doi:10.17113/ftb.54.01.16.4256

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 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.

Highlights

The prenylated chalcone xanthohumol ((E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one) is the principal prenylflavonoid of the female inflorescences of the hop plant Humulus lupulus L. [1,2]
This result strongly suggests that the toxic activity of xanthohumol is mediated by active yeast metabolism, which is attenuated in the nutrient-free phosphate-buffered saline (PBS) solution
We show that low levels of xanthohumol protect yeast cells from oxidative stress and oxidative DNA damage induced by H2O2 in a dose-dependent manner

Summary

Introduction

The prenylated chalcone xanthohumol ((E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one) is the principal prenylflavonoid of the female inflorescences (hops) of the hop plant Humulus lupulus L. [1,2]. Hops are used in beer production to add bitterness and flavour, whereby beer is the main human dietary source of xanthohumol [3,4] This phenolic compound has received considerable attention in recent years, since it has shown interesting biological properties with potential for disease prevention and therapeutic applications: anti-inflammatory, antioxidant, antilipoperoxidative activities as well as antiangiogenic and antiproliferative effects [3,4,5]. The capacity of xanthohumol to induce intracellular ROS was shown to activate the mitochondrial apoptotic pathway in human malignant glioblastoma cells [9] Other studies support this finding, showing that it is able to inhibit the growth and to induce apoptosis in several cancer cell lines: prostate [10], ovarian [11], glioblastoma and malignant astrocytes [9,12], lymphocytic leukaemia [13] and colon [14]

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