Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of and Dose Dependently in Caco-2 Cells.

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 () and the () as well as global methylation by were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on HO-induced oxidative stress. Thereby, 10 M vitamin E proved to be more efficient than did 50 M in reducing MDA. Further, an induction of and gene expression was noticed, accompanied by an increase in global methylation. Whether hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.