Dual Effect of Taxifolin on ZEB2 Cancer Signaling in HepG2 Cells.

Martin Modriansky,Martin Sebera,Zdenek Dostal,Josef Srovnal,Katerina Staffova

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.

Highlights

Polyphenols are generally secondary metabolites of plants where they play different roles such as in protection against oxidative stress, infection or UV-light [1]
We evaluated the effect of quercetin and taxifolin on viability of Hep G2 by performing
Our results show that quercetin caused toxicity at doses higher than 40 μM (Figure 1A)

Summary

Introduction

Polyphenols are generally secondary metabolites of plants where they play different roles such as in protection against oxidative stress, infection or UV-light [1]. These natural compounds are abundant in fruits, vegetables, plant derived beverages, etc., and form an important part of the human diet. Average consumption of polyphenols can exceed 1 g per day [2,3]. Their positive effects were demonstrated by many in vitro and in vivo experiments [4,5]. During the past several years many studies have described the ability of polyphenols and other natural compounds to modulate microRNA (miRNA) expression [10,11,12,13]

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Results

Conclusion