Inhibiting sirtuin-dependent DNA repair and oxidative stress responses impairs DIPG cell survival.

ABSTRACT:

Background

Diffuse intrinsic pontine gliomas (DIPG) are universally fatal pediatric brain tumors often characterized by a H3 histone mutation (H3K27M) that leads to epigenetic alterations and gene dysregulation. Histone deacetylases (HDAC), key players in modulating epigenetic pathways in cancer, have emerged as potential therapeutic targets for DIPG. This study evaluates the class III HDAC inhibitor, sirtinol, as a potential therapeutic for DIPG.

Methods

Sirtinol's efficacy and cellular mechanism were investigated using two patient-derived DIPG cell lines and one immortalized normal human astrocyte (NHAi) cell line as a comparator. Clonogenic survival was assessed under different experimental conditions, and changes in protein expression were measured via western blot and e

SUBMITTER: King SA 

PROVIDER: S-EPMC12668155 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature