Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-5810
Authors: | Kiweler, Nicole Wünsch, Désirée Wirth, Matthias Mahendrarajah, Nisintha Schneider, Günter Stauber, Roland Brenner, Walburgis Butter, Falk Krämer, Oliver |
Title: | Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes |
Online publication date: | 18-May-2021 |
Year of first publication: | 2020 |
Language: | english |
Abstract: | PURPOSE We set out to determine whether clinically tested epigenetic drugs against class I histone deacetylases (HDACs) affect hallmarks of the metastatic process. METHODS We treated permanent and primary renal, lung, and breast cancer cells with the class I histone deacetylase inhibitors (HDACi) entinostat (MS-275) and valproic acid (VPA), the replicative stress inducer hydroxyurea (HU), the DNA-damaging agent cis-platinum (L-OHP), and the cytokine transforming growth factor-β (TGFβ). We used proteomics, quantitative PCR, immunoblot, single cell DNA damage assays, and flow cytometry to analyze cell fate after drug exposure. RESULTS We show that HDACi interfere with DNA repair protein expression and trigger DNA damage and apoptosis alone and in combination with established chemotherapeutics. Furthermore, HDACi disrupt the balance of cell adhesion protein expression and abrogate TGFβ-induced cellular plasticity of transformed cells. CONCLUSION HDACi suppress the epithelial–mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-5810 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Journal of cancer research and clinical oncology 146 |
Pages or article number: | 343 356 |
Publisher: | Springer |
Publisher place: | Berlin u.a. |
Issue date: | 2020 |
ISSN: | 1432-1335 |
Publisher URL: | https://doi.org/10.1007/s00432-019-03118-4 |
Publisher DOI: | 10.1007/s00432-019-03118-4 |
Appears in collections: | JGU-Publikationen |
Files in This Item:
File | Description | Size | Format | ||
---|---|---|---|---|---|
kiweler_nicole-histone_deacet-20210422211427156.pdf | 3.54 MB | Adobe PDF | View/Open |