Gene activity regulation and new drugs

According to the concept of the young scientific discipline of epigenetics, the level of gene expression in various cells and tissues of the organism changes during the life of an individual under the influence of external and internal factors. The essence of reversible epigenetic modifications is enzymatic covalent association/dissociation of functional chemical groups to certain DNA nucleotides, as well as to amino-acid residues of histone proteins of chromatin. The two main epigenetic modifications are DNA methylation and histone deacetylation—the mechanisms that inhibit gene expression. Active studies on the role of epigenetics in the initiation and progression of malignant tumors have led to the formation of an independent scientific trend, cancer epigenetics. The number of publications that prove the epigenetic nature of proliferative diseases of organs of the reproductive system, particularly nonmalignant and precancerous pathologies of the cervix, as well as endometrium pathologies accompanied by infertility, is rapidly growing. The reversibility of anomalous epigenetic modifications makes its mediating enzymes extremely attractive medicinal targets in developing targeted epigenetic preparations. DNA methyltransferase and histone deacetylase enzymes are assumed to be the key targets. Recently, scientists have been paying increasingly more attention to nontoxic substances of natural origin with antitumor epigenetic activity. The clinical studies conducted by the authors of this paper have shown that the preparations Indinol® Forto (the active agent is indole-3-carbinol) and Epigallate® (the active agent is epigallocatechin-3-gallate) (MiraksBioFarma, Ilmix Group, Moscow), which were usually prescribed within combination therapy of nonmalignant (HPV infections) and precancerous (CIN 1–2) diseases of the cervix and pathologies of the endometrium, are effective epigenetic means that significantly demethylate and restore the activity of tumor suppressor genes, normalize the clinical picture, and ensure the absence of relapses of the above diseases a year after combination therapy. It has also been established that these preparations reverse the anomalous DNA methylation of the genes HOXA10 and HOXA11 and restore the synthesis of these genes–coded proteins, which mediate the receptivity of the endometrium in patients with infertility against the background of chronic endometritis. The proposed state-of-the-art schemes of combination therapy with the use of effective and safe epigenetically active preparations that restore the activity of tumor protection genes will become a powerful new tool for the treatment and prevention of widespread gynecological diseases, including those accompanied by infertility, and will favor qualitative improvement of the nation’s reproductive health. © 2016, Pleiades Publishing, Ltd.