Sodium valproate induces chromatin remodeling in U-251MG glioblastoma cells

The development and progression of glioblastoma, the most aggressive malignant intracranial tumor with a poor prognosis, are influenced by mutations, oncogene overexpression, and epigenetic factors, particularly those relating to DNA methylation status and histone post-translational modifications. Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, has shown promise both alone and in combination with other agents against various solid tumors, including gliomas. Given VPA's reported effects on chromatin supramolecular organization and expression activity across different cell types, we studied textural features indicative of chromatin structural changes in U-251MG glioblastoma cells cultured in the presence of VPA, utilizing image cytometry and immunofluorescence techniques. For comparison, cells treated with 5-aza-CdR served as a positive control for DNA demethylation. Chromatin remodeling was observed in VPA-treated cells, which exhibited decreased HDAC activity and increased histone H3 acetylation, whereas no such changes were detected in 5-aza-CdR-treated cells. These findings suggest that, despite alterations in DNA methylation within glioblastoma cells and a possible effect of VPA on DNA demethylation, the chromatin remodeling phenomenon observed through image cytometry in VPA-treated U-251MG cells is more closely associated with induced changes involving histone modifications rather than with DNA demethylation. Although these findings are based on in vitro conditions, present findings of basic character may acquire pre-clinical perspective implications if corroborated by further results obtained from various glioblastoma cell cultures and animal models treated with drugs that may influence epigenetic markers, while bypassing the question of blood-to-brain drug flux.