Research Article Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells Katja Zappe, 1 Angelika Pointner, 1 Olivier J. Switzeny, 2 Ulrich Magnet, 1 Elena Tomeva, 1 Jutta Heller, 1 George Mare, 1 Karl-Heinz Wagner, 1 Siegfried Knasmueller, 3 and Alexander G. Haslberger 1 1 Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria 2 Department of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany 3 Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria Correspondence should be addressed to Alexander G. Haslberger; alexander.haslberger@univie.ac.at Received 27 October 2017; Revised 18 January 2018; Accepted 29 January 2018; Published 22 March 2018 Academic Editor: Joseph Adeyemi Copyright © 2018 Katja Zappe et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l) and high (4.5 g/l) glucose cell culture condition. Malondialdehyde (MDA) as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS) was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1) and the DNA methyltransferase 1 (DNMT1) as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H 2 O 2 -induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair. 1. Introduction Lifestyle-associated diseases, such as cancer and cardiovascu- lar, respiratory, and metabolic diseases, comprise most of the noncommunicable diseases and account for more than two- thirds of the worldwide deaths [1]. Natural bioactive nutri- tional compounds like vitamin E play a major role in nutrition-based disease improvements as well as in its pre- vention [2]. Vitamin E is a collective term including α, β, γ, and δ isomers of saturated tocopherols [3] and unsaturated toco- trienols [4]. Beneficial and harmful effects on human health by vitamin E were observed, and therefore usefulness of vitamin E is highly controversial. Intervention studies showed anti-inflammatory effects, a delay of the aging process [5, 6], anticancer properties [7, 8], antidiabetic and eye disease protective potential [9], and cardiovascular protective [10] features. Adjuvant vitamin E treatment of patients suffer- ing from different cancer types led to controversial effects [11, 12]. A meta-analysis revealed an increased all-cause mor- tality by a high dose of vitamin E [13], while other studies found promising synergistic effects between vitamin E and administered drugs, especially anticancerous effects [14, 15]. Most studies are based on different isoforms of vitamin E or mixture ratios, or synthetic racemic or natural R-, E-configu- rated isomers, all leading to different biological effective doses. Hindawi Oxidative Medicine and Cellular Longevity Volume 2018, Article ID 3734250, 13 pages https://doi.org/10.1155/2018/3734250