PHARMACODYNAMICS AND INDOLE-3-CARBINOL SPECTRUM OF ACTION

Zaychenko G. V., Gorchakova N. A., Sinitsina O. S., Zaychenko V. S., Ravshanov T. B.

LITERATURE REVIEWS

Scentific article

Humans are exposed to cancerogens and is through the consumption of cruciferous vegetables that the people are able to neutralize the cancer causing agents. From the cruciferous vegetables the glucobrassicinin has been obtained and later indole-3-carbinol was produced from the hydrolysis of glucobrassin. Indole-3-carbinol has low toxicity. Indole-3-carbinol influences on the different phases of cycle in the tumor cells. Indole-3-carbinol affects several signal cascades. It inhibits different protein kinases, stimulates the production of specific inhibitors for cell division. These effects lead to the termination of cell division and interruption in the G1 phase and therefore to a halt in the dublication of chromatidis and subsequent mitosis. Indole-3-carbinol inhibits “nuclear factor cappa B” and different dependent genes. It regulates p53 gene and reduces the mitochondrial membrane potential leading to the apoptosis of cancer cells. Indole-3-carbinole influences on the prooxydative-antioxydative homeostasis, angiogenic factors-vascular endothelial growth factor, interleukin-6, matrix metalloproteinase. It reduces reactive oxygen species and increases the activity of gluthatione-S-transferase and superoxidedismutase as well as other enzymes that control oxidative status of the cells. Indole-3-carbinol influences estrogen homeostasis. Estradiol is the dominant and most effective estrogen in the human body. It is broken down into two metabolites: on the one hand to the less potent and less toxic-2-hydroxyestrone and on the other to the potent and toxic metabolite-16-alphahydroxyestrone. Indole-3-carbinol reduces conversion of estradiol into the dangerous 16-alpha-hydroxyestrone, which is regarded as tumor promoted. Indole-3-carbinol acts as direct noncompetitive inhibitor of elastase enzymatic activity: high elastase activity has been associated with late stage of breast cancer. Indole-3-carbinol triggers an elastase-dependent antiproliferate response in the10 AT-Her2 response of breast cancercell population by promoting nucleostemin to interact with and sequester the murine double mutant 2 protein into the nucleolus. It was shown the antiproliferative and anti-inflammatory properties of indole-3-carbinol. The anti-inflammatory effect was proved in the experiments with lipopolysaccharide. In the processes indole-3-carbinol inhibits the NF-kB activity as well as pro-inflammatory cytokines such as the TNF-alpha, IL-1-beta and IL-6. It was shown the effectivity of indole-3-carbinol in the cancer of hepar, lungs, prostata, in the papillomatosis of uterus, vagina, respiratory tracts. It was proved by experiments the possibility of indole-3-carbinol use in the ischemic shock, colitis. It was given the experimental and clinical data that are the basis for indole-3-carbinol use for wide spectrum of diseases treatment.

indole-3-carbinol, mechanism of antineoplastic action, anti-inflammatory, antioxidant, antithrombotic activities

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«Bulletin of problems biology and medicine» Issue 3 (145), 2018 year, 30-38 pages, index UDK 618.14-002+618.14-006.36

10.29254/2077-4214-2018-3-145-30-38