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Histone deacetylase inhibitors and genomic instability

Grégory Eot-Houllier1, Géraldine Fulcrand, Laura Magnaghi-Jaulin

  • 1Groupe Microtubules et Cycle Cellulaire, Institut de Génétique Humaine, CNRS UPR 1142, rue de la cardonille, 34396 Montpellier cedex 5, France.

Cancer Letters
|July 19, 2008
PubMed

Insights

Histone deacetylase inhibitors (HDACIs) show promise as anticancer drugs by causing genomic instability. This overlooked mechanism involves DNA damage, reactive oxygen species generation, and impaired chromosome segregation, contributing to cancer cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Histone deacetylase inhibitors (HDACIs) are emerging anticancer agents.
  • Their precise mechanisms of action, beyond gene transcription regulation, require further elucidation.
  • HDAC inhibition's impact on genomic stability is a significant, yet understudied, area.

Purpose of the Study:

  • To review the multifaceted effects of HDAC inhibitors on DNA damage and repair pathways.
  • To explore the role of HDAC inhibition in inducing genomic instability.
  • To examine the impact of HDACIs on chromosome segregation during mitosis.

Main Methods:

  • Literature review of studies investigating HDAC inhibitors.
  • Analysis of data on DNA damage and repair mechanisms modulated by HDACIs.
  • Examination of research on mitotic defects and chromosome segregation following HDACI treatment.

Main Results:

  • HDAC inhibition contributes to genomic instability through various mechanisms.
  • HDACIs sensitize cancer cells to genotoxic damage and increase reactive oxygen species production.
  • HDACIs disrupt mitosis, leading to chromosome segregation errors.

Conclusions:

  • Genomic instability is a critical, often overlooked, mechanism contributing to the anticancer effects of HDAC inhibitors.
  • Understanding these effects is crucial for optimizing HDACI-based cancer therapies.
  • HDACIs represent a promising therapeutic strategy by exploiting DNA damage and mitotic disruption pathways.

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