Dual Effect of Taxifolin on ZEB2 Cancer Signaling in HepG2 Cells

Molecules. 2021 Mar 9;26(5):1476. doi: 10.3390/molecules26051476.

Abstract

Polyphenols, secondary metabolites of plants, exhibit different anti-cancer and cytoprotective properties such as anti-radical, anti-angiogenic, anti-inflammation, or cardioprotective. Some of these activities could be linked to modulation of miRNAs expression. MiRNAs play an important role in posttranscriptional regulation of their target genes that could be important within cell signalling or preservation of cell homeostasis, e.g., cell survival/apoptosis. We evaluated the influence of a non-toxic concentration of taxifolin and quercetin on the expression of majority human miRNAs via Affymetrix GeneChip™ miRNA 3.0 Array. For the evaluation we used two cell models corresponding to liver tissue, Hep G2 and primary human hepatocytes. The array analysis identified four miRNAs, miR-153, miR-204, miR-211, and miR-377-3p, with reduced expression after taxifolin treatment. All of these miRNAs are linked to modulation of ZEB2 expression in various models. Indeed, ZEB2 protein displayed upregulation after taxifolin treatment in a dose dependent manner. However, the modulation did not lead to epithelial mesenchymal transition. Our data show that taxifolin inhibits Akt phosphorylation, thereby diminishing ZEB2 signalling that could trigger carcinogenesis. We conclude that biological activity of taxifolin may have ambiguous or even contradictory outcomes because of non-specific effect on the cell.

Keywords: Affymetrix GeneChip™ miRNA 3.0 Array; Hep G2 cells; ZEB2; polyphenols; primary cultures of human hepatocytes.

MeSH terms

  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hep G2 Cells / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • MicroRNAs / drug effects
  • MicroRNAs / genetics
  • Polyphenols / pharmacology
  • Primary Cell Culture
  • Quercetin / analogs & derivatives*
  • Quercetin / metabolism
  • Quercetin / pharmacology
  • Signal Transduction / genetics
  • Transcriptome / drug effects
  • Transcriptome / genetics
  • Zinc Finger E-box Binding Homeobox 2 / drug effects
  • Zinc Finger E-box Binding Homeobox 2 / metabolism*

Substances

  • MIRN153 microRNA, human
  • MIRN204 microRNA, human
  • MIRN211 microRNA, human
  • MIRN377 microRNA, human
  • MicroRNAs
  • Polyphenols
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Quercetin
  • taxifolin