Methyleugenol and oxidative metabolites induce DNA damage and interact with human topoisomerases

Abstract

Methyleugenol is a substituted alkenylbenzene found in several herbs and spices. It is classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed the biological mechanism of the genotoxic properties of methyleugenol and its oxidative metabolites. Methyleugenol and the oxidative metabolites significantly enhanced the DNA damage in human colon carcinoma cells (HT29). Methyleugenol did not affect the protein status of γH2AX, a biomarker of DNA double-strand breaks, whereas its metabolites methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol significantly increased the cellular phosphorylated H2AX level. Both of these metabolites also showed a significant induction of micronuclei in HT29 cells. Furthermore, we investigated whether topoisomerase interaction contribute to the observed effect on DNA integrity. Methyleugenol-2',3'-epoxide and 3'-oxomethylisoeugenol inhibited the activity of recombinant topoisomerase I. In HT29 cells, neither methyleugenol nor the metabolites affected the level of topoisomerase protein bound to DNA, excluding a topoisomerase poisoning mode of action. In addition, 3'-oxomethylisoeugenol potently diminished the level of camptothecin-stabilized topoisomerase I/DNA intermediates and camptothecin-induced DNA strand breaks. In conclusion, it could be suggested that 3'-oxomethylisoeugenol may also interact with classical or food-borne topoisomerase I poisons, diminishing their poisoning effectiveness.

Genoprotective Effects of Essential Oil Compounds Against Oxidative and Methylated DNA Damage in Human Colon Cancer Cells

“…). Methyleugenol, present in various herbs and spices and widely used in food industry, has been shown to be genotoxic in colonocytes (Groh et al., ). Linalool is a major compound in basil and coriander and has been found to be genoprotective against oxidative DNA damage in hepatocytes (Mitić‐Culafić et al., ).…”

“…Thymol and eugenol are important EOC and their genotoxicity and genoprotection against oxidative DNA damage has been demonstrated (Horváthová et al 2014). Methyleugenol, present in various herbs and spices and widely used in food industry, has been shown to be genotoxic in colonocytes (Groh et al, 2016). Linalool is a major compound in basil and coriander and has been found to be genoprotective against oxidative DNA damage in hepatocytes (Mitić-Culafić et al, 2009).…”

Chemical Interaction of Protein Cysteine Residues with Reactive Metabolites of Methyleugenol

“…The formation of DNA adduction and DNA damage induced by ME has been the focus of intensive investigations . However, relatively less effort has been directed toward the understanding of the molecular details involved in ME-derived protein covalent binding and possible toxicological significance.…”

Selected essential oils and their mechanisms for therapeutic use against public health disorders. An overview

“…Methyleugenol and its metabolites, 1′-hydroxymethyleugenol, methyleugenol-2′,3′epoxide and 3′-oxomethylisoeugenol exhibited DNA strand breaks in human colon adenocarcinoma cells HT29, whereas the metabolites showed stronger DNA damaging properties than methyleugenol itself, probably due to the high enzymatic activity of HT29 cells. Moreover, 3′-oxomethylisoeugenol was identified as topoisomerase Iand human histone deacetylase-inhibitor, which additionally contribute to DNA damage [92]. In several in vitro and in vivo studies on rodents, methyleugenol showed genotoxic and carcinogenic effects.…”