2. Academic Validation
  3. Class I HDAC Inhibition Leads to a Downregulation of FANCD2 and RAD51, and the Eradication of Glioblastoma Cells

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

  • J Pers Med. 2023 Aug 27;13(9):1315. doi: 10.3390/jpm13091315.
Małgorzata Drzewiecka 1,  Dominika Jaśniak 1,  Gabriela Barszczewska-Pietraszek 1,  Piotr Czarny 2,  Anna Kobrzycka 3,  Marek Wieczorek 3,  Maciej Radek 4,  Janusz Szemraj 2,  Tomasz Skorski 5,  Tomasz Śliwiński 1
Affiliations

Affiliations

  • 1 Laboratory of Medical Genetics Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
  • 2 Department of Medical Biochemistry, Medical University of Lodz, 92-216 Lodz, Poland.
  • 3 Department of Neurobiology, Faculty of Biology and Environmental Protection, University of Łodz, 90-236 Lodz, Poland.
  • 4 Department of Neurosurgery, Surgery of Spine and Peripheral Nerves, Medical University of Lodz, University Hospital WAM-CSW, 90-236 Lodz, Poland.
  • 5 Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
PMID: 37763083 DOI: 10.3390/jpm13091315
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.

Keywords

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

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16106
    99.89%, PARP Inhibitor