Class I HDAC Inhibition Leads to a Downregulation of FANCD2 and RAD51, and the Eradication of Glioblastoma Cells

Małgorzata Drzewiecka, Dominika Jaśniak, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Anna Kobrzycka, Marek Wieczorek, Maciej Radek, Janusz Szemraj, Tomasz Skorski, Tomasz Śliwiński

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme. At the molecular level, VPA leads to a downregulation of FANCD2 and RAD51, and the eradication of glioblastoma cells. The results of this study indicate that combining HDACi with PARPi could potentially enhance the treatment of glioblastoma, the most aggressive type of cancer that originates in the brain.

Original languageEnglish
Article number1315
JournalJournal of Personalized Medicine
Volume13
Issue number9
DOIs
StatePublished - Jul 27 2023

Keywords

  • DNA damage response
  • double-strand break
  • glioblastoma multiforme
  • HDAC
  • synthetic lethality
  • valproic acid

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