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

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Abstract
The development and progression of glioblastoma, the most aggressive malignant intracranial tumor with a poor prognosis, are influenced by mutations, the overexpression of oncogenes, and epigenetic factors, particularly those related to DNA methylation status and histone post-translational modifications. Valproic acid (VPA), a classic histone deacetylase (HDAC) inhibitor, has shown promise both on its own and in combination with other drugs as a therapeutic agent against various solid tumors, including gliomas. Given VPA’s reported effects on chromatin supraorganization and expression activity in several cell types, we studied textural features that may indicate changes in chromatin structure in U-251MG glioblastoma cells cultured in the presence of VPA, utilizing image cytometry. 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 displayed 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 the significance of DNA methylation alterations in glioblastoma cells, the chromatin remodeling 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.
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