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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 3734250, 13 pages
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

1Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria
2Department of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
3Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria

Correspondence should be addressed to Alexander G. Haslberger;

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 H2O2-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.