@article{17f6caa1424a4723816f7ad970316c6e,
title = "Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes",
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.",
keywords = "Adhesion, DNA damage, EMT, HDACi, MET, TGFβ",
author = "Nicole Kiweler and D{\'e}sir{\'e}e W{\"u}nsch and Matthias Wirth and Nisintha Mahendrarajah and G{\"u}nter Schneider and Stauber, {Roland H.} and Walburgis Brenner and Falk Butter and Kr{\"a}mer, {Oliver H.}",
note = "Funding Information: Open Access funding provided by Projekt DEAL. We thank Franziska M{\"u}ller, Christina Brachetti, and Andrea Pi{\'e}e-Staffa (ITOX Mainz, Germany) for excellent technical support; Mandy Beyer (ITOX Mainz, Germany) for help with statistics; Dr. Mario Dejung (IMB Mainz, Germany) for help with proteomics. We are indebted to Prof. W. Wels, GSH Frankfurt/Main, Germany, Dr. G. Rohaly, HPI, Hamburg, Germany, and Deckers and colleagues, University Medical Center, Leiden, The Netherlands, for cell lines. This study was mainly supported by grants to OHK from the Wilhelm Sander-Stiftung (#2010.078). The group of OHK is additionally supported by the Deutsche Forschungsgemeinschaft (#KR2291/7-1/8-1/9-1), funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project-ID 393547839 – SFB 1361, and received intramural funding from the NMFZ Mainz and the University Medical Center Mainz. Funding Information: Open Access funding provided by Projekt DEAL. We thank Franziska M?ller, Christina Brachetti, and Andrea Pi?e-Staffa (ITOX Mainz, Germany) for excellent technical support; Mandy Beyer (ITOX Mainz, Germany) for help with statistics; Dr. Mario Dejung (IMB Mainz, Germany) for help with proteomics. We are indebted to Prof. W. Wels, GSH Frankfurt/Main, Germany, Dr. G. Rohaly, HPI, Hamburg, Germany, and Deckers and colleagues, University Medical Center, Leiden, The Netherlands, for cell lines. This study was mainly supported by grants to OHK from the Wilhelm Sander-Stiftung (#2010.078). The group of OHK is additionally supported by the Deutsche Forschungsgemeinschaft (#KR2291/7-1/8-1/9-1), funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) ? Project-ID 393547839 ? SFB 1361, and received intramural funding from the NMFZ Mainz and the University Medical Center Mainz. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = feb,
day = "1",
doi = "10.1007/s00432-019-03118-4",
language = "English",
volume = "146",
pages = "343--356",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "2",
}