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

Abstract

SummaryThe eff ect of xanthohumol, a prenylfl avonoid 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 H 2 O 2 , displayed stronger growth in the presence of 5 mg/L of xanthohumol than cultures with only H 2 O 2 . Likewise, DNA damage assessed by the comet assay was signifi cantly lower in cells co-incubated with xanthohumol and H 2 O 2 . Accordingly, fl uorescence of dichlorofl uorescein in cells treated with H 2 O 2 and xanthohumol was considerably lower than in cells exclusively treated with H 2 O 2 , 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 eff ect, 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 eff ects.

Antioxidant and pro-oxidant phytochemicals in ultrasound and microwave assisted extracts from hop cones: a statistical modelling approach

“…9 As far as hop is concerned, Strathmann et al demonstrated that XH induces ROS production, 10 which disrupts the cellular redox balance and mitochondrial integrity and subsequently triggers cancer cells into apoptosis. These findings are also supported by the results of Carvalho et al , 11 who strongly suggested that XH toxicity is mediated by oxidative stress, having a dose-dependent dual effect on yeast cells. The capacity of XH to decrease cell viability in a dose-dependent manner has also been reported in different tumorigenic cell lines.…”

The Multiple Biological Targets of Hops and Bioactive Compounds

“…Hops contain many prenylated aromatic compounds, such as 8-PN and XH, that can act as scavengers of reactive oxygen species (ROS) and prevent oxidative damage to proteins and DNA. − The data suggest that the prenylated phenols in particular can protect cellular proteins such as low-density lipoproteins (LDL) from oxidation . Similar protective effects on DNA oxidation have been reported, especially for XH. , XH could be an indirect antioxidant by increasing GSH. A small clinical study where participants consumed a drink containing XH (12 mg/day) showed a significant drop in 8-oxo-2′-deoxyguanosine (8-oxo-dG) levels, a biomarker of hydroxy radical induced oxidative DNA damage .…”

“…53 Similar protective effects on DNA oxidation have been reported, especially for XH. 54,55 XH could be an indirect antioxidant by increasing GSH. A small clinical study where participants consumed a drink containing XH (12 mg/day) showed a significant drop in 8-oxo-2′deoxyguanosine (8-oxo-dG) levels, a biomarker of hydroxy radical induced oxidative DNA damage.…”

Oxidative Stress Parameters in the Liver of Growing Male Rats Receiving Various Alcoholic Beverages

“…So far, no studies have been published assessing the influence of specific components of beer on the process of protein oxidation, so it would be valuable to specify which polyphenolic compounds of beer may be responsible for this activity. However, some suggestions can be formulated based on the in vitro study by Carvalho et al [44], which showed that lower doses of xanthohumol protected the DNA of yeast cells against oxidative damage, whereas higher doses exerted a pro-oxidative effect. Therefore, it may be concluded that xanthohumol may have caused the pro-oxidative action that was observed after prolonged consumption of beer.…”