DNA Methylation Status in Cancer Disease: Modulations by Plant-Derived Natural Compounds and Dietary Interventions

Abstract

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.

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

“…It is well described that epigenetic alterations dynamically contribute to cancer pathogenesis [80]. Numerous phytochemicals with antitumor properties have also shown a significant effect on epigenome of neoplastic cells [10][11][12]. Therefore, the role of a diet rich in phytochemicals and its impact on the cancer epigenome is a clinically highly relevant topic.…”

“…Moreover, many plant-derived substances have been proved to regulate the cell cycle, programmed cell death, angiogenesis, and activity of stem cells in cancer tissue and thus may suppress the growth and spread of malignant cells in organisms [8,9]. In addition, the tumor-suppressive potential of plant bioactive molecules also includes intensively discussed targeting of the aberrant epigenetic modifications particularly on the level of the global DNA hypomethylation status of the cells, hypermethylation of tumor suppressor gene promoters, histone post-translational modifications, and non-coding RNA (ncRNA)-linked multi-gene network modulations [10][11][12][13]. However, regarding clinical research, only a relatively limited number of epidemiological studies and meta-analyses have documented that regular (4-5 times a week) and long-term (several years) consumption of selected whole plant foods (not isolated molecules) is significantly associated with a decrease in cancer risk, including breast carcinoma (BC) [14][15][16][17].…”

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…Actually, the anti-cancer effectiveness of selected phytochemicals can be supported by an amount of evidence suggesting an important role of whole plant foods. Due to the presence of mixture of phytochemicals, whole plant food is suggested to exert better anti-cancer abilities when compared with isolated phytochemicals [96][97][98]. Therapeutic potential of whole plant food was demonstrated by several studies including evaluation of administration of Vaccinium myrtillus extract with GeA as the most abundant polyphenol [16], as well as RVSE with identified presence of GA [28].…”

Anticancer Potential of Lichens’ Secondary Metabolites

“…Numerous biomolecules derived from plants are also capable of synergizing with chemoand radiotherapy. Such a combination can potentially lead to the increase of therapeutic effects and/or can reduce the side effects because lower doses of conventional therapeutics are needed [10][11][12][13][14][15].…”