DNA methylation is one of the mechanisms of epigenetic regulation of gene expression. Upon methylation of cytosine residues (within the sequence 5’CpG3’), the affected sequence is bound by methylated DNA binding proteins (MBDs) and forms compact chromatin. Short stretches of DNA which are rich in CpG dinucleotides are called CpG islands. They are present in promoters of over a half of human genes and are normally not methylated. Cancer cells are characterized by aberrant methylation of such CpG islands, which is a frequent mechanism of silencing of tumor suppressor genes, while other sequences (especially repetitive sequences) are undermethylated.

Aberrant methylation is detected as soon as in precancerous lesions and contributes to the development of tumors. The benefit of gene loss through cytosine methylation, in contrast to mutations, is that the process can be reversed upon blocking of the enzymes that catalyze cytosine methylation- DNA methyltransferases (DNMTs). There are three major isoforms of DNMTs: DNMT1, DNMT3a, DNMT3b and there is an ongoing debate which isoform is responsible for forming aberrant methylation patterns in cancer. It seems that different tumor cells may require different isoforms for aberrant methylation.

As the process of aberrant methylation starts at very early stages of cancer development, it is reasonable to consider it a good target for chemoprevention. Chemoprevention is a strategy of preventing, blocking or even reversing cancer development through the use of natural or synthetic compounds which are capable of modulation of different processes leading to cancer. It was proved that inhibition of DNA methylation prevents the formation of tumors in a mouse model of lung cancer. A few natural compounds (e.g. chlorogenic acid, caffeic acid, genistein, epigallocatechin gallate, myricetin) are known to possess the activity of inhibition of DNA methyltransferases but there is still a necessity of finding other compounds and determination of structure-activity relationships.

The aim of this study was to assess the influence of a set of natural phenolic compounds with different chemical structures: myricetin, cyanidin, phloretin, baicalein, galangin, xanthohumol, resveratrol, piceatannol, protocatechuic acid, ellagic acid, sinapic acid, syringic acid, rosmarinic acid and betanin on the activity of DNA methyltfansferases in MCF7 breast cancer cells. Nuclear extracts containing DNMTs were prepared from MCF7 cells according to standard protocols. The activity of DNMTs in the presence of three different concentrations of each compound (50 μM, 20 μM or 10 μM) was determined using a colorimetric ELISA kit from Epigentek.

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