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Dual Effect of Taxifolin on ZEB2 Cancer Signaling in HepG2 Cells
Z. Dostal, M. Sebera, J. Srovnal, K. Staffova, M. Modriansky
Language English Country Switzerland
Document type Journal Article
Grant support
RVO 61989592
Ministry of Education of the Czech Republic
IGA_LF_2020_022
Palacký University
NLK
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- MeSH
- Apoptosis drug effects MeSH
- Hep G2 Cells metabolism MeSH
- Epithelial-Mesenchymal Transition genetics MeSH
- Gene Expression drug effects genetics MeSH
- Hepatocytes drug effects metabolism MeSH
- Humans MeSH
- MicroRNAs drug effects genetics MeSH
- Cell Movement drug effects MeSH
- Polyphenols pharmacology MeSH
- Primary Cell Culture MeSH
- Cell Proliferation drug effects MeSH
- Quercetin analogs & derivatives metabolism pharmacology MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- Signal Transduction genetics MeSH
- Zinc Finger E-box Binding Homeobox 2 drug effects metabolism MeSH
- Transcriptome drug effects genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
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.
References provided by Crossref.org
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