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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
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
Version: Published version
Publication type: Zeitschriftenaufsatz
Document type specification: Scientific article
License: CC BY
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Journal: Journal of cancer research and clinical oncology
Pages or article number: 343
Publisher: Springer
Publisher place: Berlin u.a.
Issue date: 2020
ISSN: 1432-1335
Publisher URL:
Publisher DOI: 10.1007/s00432-019-03118-4
Appears in collections:JGU-Publikationen

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