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Updated: Nov 7, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Vorinostat exhibits anticancer effects in triple-negative breast cancer cells by preventing nitric oxide-driven

Marianne B Palczewski1, Hannah Petraitis Kuschman1, Rhea Bovee2

  • 1Department of Pharmaceutical Sciences, University of Illinois at Chicago, 833 S. Wood Street, Chicago, IL 60607, USA.

Biological Chemistry
|May 3, 2021
PubMed

Insights

Nitric oxide (NO) promotes aggressive triple-negative breast cancer (TNBC) growth. The histone deacetylase inhibitor Vorinostat (SAHA) counteracts NO-induced proliferation by restoring histone acetylation, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) is aggressive, with nitric oxide (NO) production and inducible nitric oxide synthase (NOS2) expression indicating poor prognosis.
  • NO promotes TNBC cell proliferation, highlighting the need for therapeutic strategies to counteract its tumor-promoting effects.

Purpose of the Study:

  • To investigate therapeutic strategies targeting NO-driven TNBC aggressiveness.
  • To elucidate the molecular mechanisms underlying NO's effect on TNBC cell proliferation and histone acetylation.

Main Methods:

  • TNBC cell lines were exposed to NO and/or the histone deacetylase inhibitor Vorinostat (SAHA).
  • Cell proliferation was measured, and histone acetylation levels (H3K9ac) were assessed using biochemical assays.
  • Mechanistic studies explored NO's interaction with cellular iron pools and histone methylation.

Main Results:

  • NO exposure significantly increased TNBC cell proliferation.
  • SAHA treatment prevented NO-induced proliferation and increased H3K9ac.
  • NO decreased H3K9ac, an effect dependent on cellular iron pools and potentially overridden by histone methylation.

Conclusions:

  • Vorinostat (SAHA) demonstrates therapeutic potential against aggressive TNBC by reversing NO-mediated suppression of histone acetylation.
  • This study reveals a novel interaction pathway involving Vorinostat, NO, and histone modifications, offering new insights for TNBC treatment strategies.
Keywords:
chemotherapyepigeneticsfree radicalspost-translational modificationsproliferation

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