Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

• DOI: 10.1007/s00432-019-03118-4
• Publication Date: 2020-01-13T08:02:43Z
• Authors: Nicole Kiweler; Désirée Wünsch; Matthias Wirth; Nisintha Mahendra...; Günter Schneider; Roland H. Stauber; Walburgis Brenner; Falk Butter; Oliver H. Krämer
• Keywords: Histone deacetylase inhibitor; Histone deacetylase 5

We set out to determine whether clinically tested epigenetic drugs against class I histone deacetylases (HDACs) affect hallmarks of the metastatic process.We treated permanent and primary renal, lung, breast cancer cells with deacetylase inhibitors (HDACi) entinostat (MS-275) valproic acid (VPA), replicative stress inducer hydroxyurea (HU), DNA-damaging agent cis-platinum (L-OHP), cytokine transforming growth factor-β (TGFβ). used proteomics, quantitative PCR, immunoblot, single cell DNA damage assays, flow cytometry analyze fate after drug exposure.We show that HDACi interfere repair protein expression trigger apoptosis alone in combination established chemotherapeutics. Furthermore, disrupt balance adhesion abrogate TGFβ-induced cellular plasticity transformed cells.HDACi suppress epithelial-mesenchymal transition (EMT) compromise integrity cells. These data encourage further testing tumor