ArticleScientific reports2019
Sodium valproate and 5-aza-2'-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
- A Novel Epigenetic Mechanism of Intestinal NHE3 Gene Regulation by Histone Acetylation.International journal of molecular sciences · 2026Article
- Effects of DNMT1 and TET2 on proliferation and differentiation of goose embryonic myoblasts.Poultry science · 2025Article
- GLUT1 and Cerebral Glucose Hypometabolism in Human Focal Cortical Dysplasia Is Associated with Hypermethylation of Key Glucose Regulatory Genes.Molecular neurobiology · 2025Article
- Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.Biomolecules & therapeutics · 2025Article
- Sodium valproate affects the expression of p16Oncology letters · 2024Article
- Impact of high-fat diet on ovarian epigenetics: Insights from altered intestinal butyric acid levels.Heliyon · 2024Article
- Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.Current neuropharmacology · 2024Review
- Nuclear Morphofunctional Organization and Epigenetic Characteristics in Somatic Cells ofPathogens (Basel, Switzerland) · 2023Review
- Knockdown ofInternational journal of molecular sciences · 2022Article
- Untargeted Metabolomics Showed Accumulation of One-Carbon Metabolites to Facilitate DNA Methylation during Extracellular Matrix Detachment of Cancer Cells.Metabolites · 2022Article
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- Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain.Cellular and molecular neurobiology · 2021Article
- Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways.Scientific reports · 2021Article
- Sodium Valproate-Induced Chromatin Remodeling.Frontiers in cell and developmental biology · 2021Review
- Cancer and Tumour Suppressor p53 Encounters at the Juncture of Sex Disparity.Frontiers in genetics · 2021Review
- A medicinal chemistry perspective of drug repositioning: Recent advances and challenges in drug discovery.European journal of medicinal chemistry · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sodium valproate/valproic acid (VPA), a histone deacetylase inhibitor, and 5-aza-2-deoxycytidine (5-aza-CdR), a DNA methyltransferase 1 (DNMT1) inhibitor, induce DNA demethylation in several cell types. In HeLa cells, although VPA leads to decreased DNA 5-methylcytosine (5mC) levels, the demethylation pathway involved in this effect is not fully understood. We investigated this process using flow cytometry, ELISA, immunocytochemistry, Western blotting and RT-qPCR in G1 phase-arrested and proliferative HeLa cells compared to the presumably passive demethylation promoted by 5-aza-CdR. The results revealed that VPA acts predominantly on active DNA demethylation because it induced TET2 gene and protein overexpression, decreased 5mC abundance, and increased 5-hydroxy-methylcytosine (5hmC) abundance, in both G1-arrested and proliferative cells. However, because VPA caused decreased DNMT1 gene expression levels, it may also act on the passive demethylation pathway. 5-aza-CdR attenuated DNMT1 gene expression levels but increased TET2 and 5hmC abundance in replicating cells, although it did not affect the gene expression of TETs at any stage of the cell cycle. Therefore, 5-aza-CdR may also function in the active pathway. Because VPA reduces DNA methylation levels in non-replicating HeLa cells, it could be tested as a candidate for the therapeutic reversal of DNA methylation in cells in which cell division is arrested.
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