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Assays for Validating Histone Acetyltransferase Inhibitors
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Histone deacetylase inhibitors disrupt the mitotic spindle assembly checkpoint by targeting histone and nonhistone

Brian Gabrielli1, Mellissa Brown

  • 1The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia. brianG@uq.edu.au

Advances in Cancer Research
|October 24, 2012
PubMed

Insights

Histone deacetylase inhibitors disrupt cell division, promoting cancer cell death by overriding the mitotic spindle assembly checkpoint. This leads to apoptosis through direct protein target regulation, not transcriptional changes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Pharmacology

Background:

  • Histone deacetylase inhibitors (HDACi) have diverse effects on cellular functions.
  • A key anticancer mechanism of HDACi involves disruption of mitotic division.

Purpose of the Study:

  • To elucidate the mechanisms by which HDAC inhibitors impact mitosis.
  • To identify specific protein targets affected by HDAC inhibitors during cell division.

Main Methods:

  • Investigated the effects of HDAC inhibitors on mitotic progression in vitro and in vivo.
  • Identified chromatin and non-chromatin protein targets regulated by acetylation/deacetylation.

Main Results:

  • HDAC inhibitors overcome the mitotic spindle assembly checkpoint, inducing mitotic slippage and apoptosis.
  • Mitotic disruption is mediated by direct or indirect acetylation/deacetylation of critical regulatory proteins.
  • Transcriptional changes play a minimal role in the observed mitotic effects.

Conclusions:

  • HDAC inhibitors induce apoptosis by disrupting mitosis through specific protein target modulation.
  • The anticancer effects of HDAC inhibitors are primarily due to direct interference with mitotic progression.

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