Фармакокинетика и Фармакодинамика (Mar 2018)

Dose-dependent chemotranscriptomics analysis of the differential effects of vitamin D<sub>3</sub> on gene expression in human neuronal progenitor cells NPC and in MCF7 tumor cells

  • I. Yu. Torshin,
  • O. A. Gromova,
  • D. E. Frolova,
  • T. R. Grishina,
  • N. P. Lapochkina

DOI
https://doi.org/10.24411/2587-7836-2018-10013.
Journal volume & issue
Vol. 0, no. 2
pp. 35 – 51

Abstract

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Resume. Different cell types respond differently to the effects of vitamin D3. The paper presents the results of a dose-dependent differential chemotranscriptome analysis of vitamin D3 in relation to breast tumor cells (MCF7 line) and neuron progenitor cells (NPC line). Expression of the genes involved in immunomodulation (192 genes) was significantly increased in tumor cells and in the intracellular signaling from receptors (275 genes) and the expression of genes involved in maintaining energy metabolism (482 genes), cell division / proliferation (387 genes), DNA repair (391 gene), synthesis and transport of proteins (188 genes) and in maintaining chronic inflammation (factors of TNF / NF-kB. 105 genes). In neuronal cells, similar changes in the expression of these categories of genes occurred to a much lesser extent and did not reach statistical significance. The reduction in DNA repair in tumor cells stimulates their apoptosis, the decrease in energy metabolism reduces the ability of tumor cells to divide and to resist therapeutic effects. It is interesting to note that vitamin D3 contributed to a decrease in the expression of genes supporting the cellular response to gamma radiation (9 genes) and contributed to the enhancement of the antitumor effects of vitamin A (5 genes). Also, vitamin D3 reduced the expression of genes that express potential target proteins of antitumor drugs (casein kinase, c-src tyrosine kinase, c-myc, etc.). Thus, vitamin D3 suppressed the division of tumor cells in a dose-dependent manner, without adversely affecting the survival of neurons.

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