Gene Activity Regulation and New Drugs

Paper by RAS Corresponding Member V. I. Kiselev^a and RAS Academician M. A. Pal’tsev^b,c *

^a Institute of Medical–Biological Problems, Peoples’ Friendship University of Russia, Moscow, Russia

^b Presidium of the Russian Academy of Sciences, Moscow, Russia

^c Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia

e-mail: vkis10@mail.ru, paltsev@presidium.ras.ru

Received January 20, 2016

Abstract—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 meth-
ylation 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 pro-
teins, 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 epigeneti-
cally 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.

Keywords: epigenetic regulation, DNA methylation, cervical diseases, pathological process of the
endometrium, endometrium receptivity, infertility.

The 20th century saw the triumph of genetics. The current century,
no doubt, will by right be considered the age of epigenetics.

RAS Corresponding Member B.F. Vanyushin

Genetics proposes; epigenetics disposes.

Nobel Prizewinner P.B. Medawar

DOI: 10.1134/S1019331616030126

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