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Assays for Validating Histone Acetyltransferase Inhibitors
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Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

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

Nicole Kiweler1,2, Désirée Wünsch3, Matthias Wirth4,5

  • 1Department of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 67, 55131, Mainz, Germany.

Journal of Cancer Research and Clinical Oncology
|January 15, 2020
PubMed
Abstract

Insights

Epigenetic drugs targeting histone deacetylases (HDACs) inhibit cancer cell DNA repair and plasticity, suppressing metastasis. These HDAC inhibitors show promise for further cancer therapy development.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Metastasis is a complex process involving cellular plasticity and DNA integrity.
  • Histone deacetylases (HDACs) play a role in cancer progression.
  • Epigenetic drugs targeting HDACs are under clinical investigation.

Purpose of the Study:

  • To investigate the effect of class I histone deacetylase inhibitors (HDACi) on the hallmarks of cancer metastasis.
  • To determine if clinically tested epigenetic drugs impact key metastatic processes.

Main Methods:

  • Treatment of renal, lung, and breast cancer cells with HDAC inhibitors (entinostat, VPA), hydroxyurea, cis-platinum, and TGF-β.
  • Analysis of cellular response using proteomics, qPCR, immunoblot, DNA damage assays, and flow cytometry.

Main Results:

  • HDAC inhibitors interfere with DNA repair protein expression, inducing DNA damage and apoptosis.
  • HDAC inhibitors disrupt cell adhesion protein balance and abrogate TGF-β-induced cellular plasticity.
  • HDAC inhibitors suppress epithelial-mesenchymal transition (EMT) and compromise cancer cell DNA integrity.

Conclusions:

  • Class I HDAC inhibitors suppress key metastatic processes, including EMT and cellular plasticity.
  • HDAC inhibitors compromise cancer cell DNA integrity, leading to apoptosis.
  • These findings support further clinical evaluation of HDAC inhibitors in cancer treatment.
Keywords:
AdhesionDNA damageEMTHDACiMETTGFβ

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