Class I HDAC Inhibition Leads to a Downregulation of FANCD2 and RAD51, and the Eradication of Glioblastoma Cells.
Malgorzata DrzewieckaDominika JaśniakGabriela Barszczewska-PietraszekPiotr Lech CzarnyAnna KobrzyckaMarek WieczorekMaciej RadekJanusz Zbigniew SzemrajTomasz SkorskiTomasz SliwińskiPublished in: Journal of personalized medicine (2023)
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.
Keyphrases
- dna damage
- histone deacetylase
- induced apoptosis
- dna repair
- papillary thyroid
- cell cycle arrest
- cell proliferation
- oxidative stress
- signaling pathway
- dna methylation
- squamous cell carcinoma
- single molecule
- helicobacter pylori infection
- squamous cell
- cell death
- white matter
- resting state
- gene expression
- circulating tumor
- lymph node metastasis
- pi k akt
- childhood cancer
- anti inflammatory
- combination therapy
- smoking cessation