ArticleResearch square2025
Inhibiting sirtuin-dependent DNA repair and oxidative stress responses impairs DIPG cell survival.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
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 enzymatic assays. Liquid chromatography tandem mass spectrometry (LC-MS-MS) was used to measure brain and blood penetrance of sirtinol in mice. Results: We found that sirtinol dose-dependently decreased clonogenic cell survival in DIPG cells while having negligible effects on NHAi cells. Combined treatment of sirtinol and radiation resulted in additive toxicity in DIPG, but not NHAi cells. Sirtinol was less toxic in DIPG cells overexpressing mitochondrial-targeted catalase, suggesting peroxide generation as one mode of cell killing. Moreover, sirtinol was found to increase DNA double strand breaks in DIPG cells and decrease phosphorylation of SIRT2-mediated DNA repair pathway kinase ataxia-telangiectasia and Rad3-related protein (ATR). Sirtinol was detected in the brains of sirtinol-treated mice, suggesting blood brain barrier penetrance. Conclusions: Based on our results, sirtinol shows promise as a selective, redox-modulating therapeutic for DIPG that enhances oxidative stress and interferes with DNA repair.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.