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Curcumin as a modifier of histone methylating enzymes expression

It has been known for a long time that a healthy lifestyle, which includes a healthy diet, decreases the risk of cancer. Among many different spices which are scientifically proved to have antitumorous potential, curcumin is probably the best studied. Research being done in South-East Europe is in its earliest stages. We are convienced that curcumin influences the epigenome network of a cell, as the basis for its cancer preventive action From an epigenomic point of view, cancer is a disease of dysregulated genes functioning. This is a well- known consequence of several different cellular processes, of which aberrant DNA methylation and histone modifications play very important roles. Our particular scientific interest in cancer research focuses on specific histone modification, H3 Lysine-27 trimethylation, H3K27me3, which was shown to be present in the promoter regions of different tumor suppressor genes, leading to their silencing. Two enzymes are critical for creating and erasing this potent epigenomic mark. The histone methyltransferase, EZH2 (enhancer of zeste homologue) constitutes the catalytic component of the polycomb repressive complex-2 (PRC2) and is the key enzyme in Lysine-27 trimethylation process. Histone-27 demethylase JMJD3 acts in the opposite direction, through binding to PRC2 target genes promoters, where it regulates their H3K27me3 level and, consequentially, their transcriptional activity. We have explored the influence of different concentrations of curcumin on EZH2 gene expression/activity through measuring its expression by qRT-PCR, Western blot and immunocytochemistry in two different cancer cell lines. Additional experiments, performed on JMJD3 gene activity through RT-PCR, have shown how, upon treatment with curcumin, the balance between EZH2 and JMJD3 transcripts dramatically changes. In light of these discoveries, several possible scenarios for cancer prevention will be discussed.

curcumin; EZH2; JMJD3; expression; epigenetics

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