Autoren:	Kiweler, Nicole Wünsch, Désirée Wirth, Matthias Mahendrarajah, Nisintha Schneider, Günter Stauber, Roland Brenner, Walburgis Butter, Falk Krämer, Oliver
Titel:	Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes
Online-Publikationsdatum:	18-Mai-2021
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5810
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart:	Scientific article
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Journal of cancer research and clinical oncology 146
Seitenzahl oder Artikelnummer:	343 356
Verlag:	Springer
Verlagsort:	Berlin u.a.
Erscheinungsdatum:	2020
ISSN:	1432-1335
URL der Originalveröffentlichung:	https://doi.org/10.1007/s00432-019-03118-4
DOI der Originalveröffentlichung:	10.1007/s00432-019-03118-4
Enthalten in den Sammlungen:	JGU-Publikationen