MicroRNA hsa-miR-29 was connected to a number of malignancies. Its target genes are many, among them Mcl-1 that is expressed in three possible isoforms, one of which is anti-apoptotic and another one pro-apoptotic. Ratio of these two isoforms appears to affect cell response to external stimuli. We have demonstrated that miR-29b enhanced etoposide toxicity in HeLa cell line by modulating this ratio of Mcl-1 isoforms. However, it is not known whether the described miR-29 effect is common to various cancer types or even have the opposite effect. This represents a significant problem for possible future applications. In this report, we demonstrate that miR-29b affects toxicity of 60 μM etoposide in cell lines derived from selected malignancies. The mechanism, however, differs among the cell lines tested. Hep G2 cells demonstrated similar effect of miR-29b on etoposide toxicity as was described in HeLa cells, i.e. modulation of Mcl-1 expression. Target protein down-regulated by miR-29b resulting in enhanced etoposide toxicity in Caco-2 cells was, however, Bcl-2 protein. Moreover, H9c2, Hek-293 and ARPE-19 cell lines selected as a representatives of non-malignant cells, showed no effect of miR-29b on etoposide toxicity. Our data suggest that miR-29b could be a common enhancer of etoposide toxicity in malignant cells due to its modulation of Bcl family proteins.

• MeSH
• Apoptosis drug effects   genetics   MeSH
• Hep G2 Cells MeSH
• Caco-2 Cells MeSH
• Etoposide * toxicity   pharmacology   MeSH
• Antineoplastic Agents, Phytogenic pharmacology   toxicity   MeSH
• HEK293 Cells MeSH
• HeLa Cells MeSH
• Humans MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Myeloid Cell Leukemia Sequence 1 Protein * genetics   metabolism   MeSH
• Proto-Oncogene Proteins c-bcl-2 genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Etoposide * MeSH
• Antineoplastic Agents, Phytogenic MeSH
• MCL1 protein, human MeSH Browser
• MicroRNAs * MeSH
• MIRN29a microRNA, human MeSH Browser
• Myeloid Cell Leukemia Sequence 1 Protein * MeSH
• Proto-Oncogene Proteins c-bcl-2 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.

• Keywords
• Affymetrix GeneChip™ miRNA 3.0 Array, Hep G2 cells, ZEB2, polyphenols, primary cultures of human hepatocytes,
• 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
• Names of Substances
• MicroRNAs MeSH
• MIRN153 microRNA, human MeSH Browser
• MIRN204 microRNA, human MeSH Browser
• MIRN211 microRNA, human MeSH Browser
• MIRN377 microRNA, human MeSH Browser
• Polyphenols MeSH
• Quercetin MeSH
• taxifolin MeSH Browser
• Zinc Finger E-box Binding Homeobox 2 MeSH
• ZEB2 protein, human MeSH Browser