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Updated: Nov 3, 2025

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

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Effect of the HDAC Inhibitor on Histone Acetylation and Methyltransferases in A2780 Ovarian Cancer Cells

Umamaheswari Natarajan1, Thiagarajan Venkatesan1, Appu Rathinavelu1,2

  • 1Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL 33314, USA.

Medicina (Kaunas, Lithuania)
|June 2, 2021
PubMed

Insights

The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) reduces DNA methyltransferases in ovarian cancer cells by increasing histone acetylation. This epigenetic interplay may improve cancer treatment outcomes.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Epigenetic modifications are crucial in cancer development, influencing progression, growth, differentiation, and cell death.
  • Histone deacetylase inhibitors (HDACIs) like suberoylanilide hydroxamic acid (SAHA) activate p21 gene transcription via histone hyperacetylation, independent of p53.
  • Understanding the interplay between histone modifications and DNA methyltransferases is vital for cancer therapy.

Purpose of the Study:

  • To investigate the correlation between histone modifications and DNA methyltransferase levels after SAHA treatment in A2780 ovarian cancer cells.
  • To elucidate the impact of SAHA-induced histone hyperacetylation on methyltransferase enzyme activity.
  • To explore potential therapeutic implications of these epigenetic changes in ovarian cancer.

Main Methods:

  • Utilized RT2 profiler PCR array, immunoblotting, and immunofluorescence assays.
  • Analyzed histone acetylation and methyltransferase levels in 2D and 3D cell culture models.
  • Investigated SAHA's effects on A2780 ovarian cancer cells.

Main Results:

  • SAHA treatment inhibited histone deacetylase (HDAC) activity, leading to histone hyperacetylation.
  • SAHA significantly reduced DNA methyltransferases/histone methyltransferases (DNMTs/HMTs) levels.
  • Immunofluorescence confirmed increased histone acetylation precedes the reduction in methyltransferase levels in both monolayer and spheroid cultures.

Conclusions:

  • SAHA induces histone hyperacetylation, which correlates with decreased methyltransferase levels in ovarian cancer cells.
  • This epigenetic interplay suggests a potential mechanism for enhancing ovarian cancer treatment efficacy.
  • Findings highlight a novel therapeutic strategy targeting epigenetic regulators in ovarian cancer.
Keywords:
DNA methyltransferaseSAHAepigenetic alterationshistone modificationsp21WAF1/CIP1

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