The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans.

Department of Anatomy Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Histology and Embryology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Immunology School of Medicine Keimyung University Dalseo Gu Daegu 426 01 Korea

Department of Medical Biology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Natural Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences 612 42 Brno Czech Republic

Department of Obstetrics and Gynecology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Division of Oncology Biomedical Center Martin Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Lambda Life JSC 851 01 Bratislava Slovakia

Weill Cornell Medicine in Qatar Qatar Foundation Education City Doha 24144 Qatar

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