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 establ

SUBMITTER: Kiweler N 

PROVIDER: S-EPMC6985217 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature