ArticleClinical epigenetics2016
Vitamin C enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7.
Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 60 citations in OpenAlex.
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- Mitoepigenetics and gliomas: epigenetic alterations to mitochondrial DNA and nuclear DNA alter mtDNA expression and contribute to glioma pathogenicity.Frontiers in neurology · 2023Review
- Vitamin C Suppresses Pancreatic Carcinogenesis through the Inhibition of Both Glucose Metabolism and Wnt Signaling.International journal of molecular sciences · 2022Article
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- Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma.International journal of biological sciences · 2022Article
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- Epigenetic Deregulation of the Histone MethyltransferaseFrontiers in cell and developmental biology · 2021Article
- TET is targeted for proteasomal degradation by the PHD-pVHL pathway to reduce DNA hydroxymethylation.The Journal of biological chemistry · 2020Article
- Chlorogenic Acid Decreases Malignant Characteristics of Hepatocellular Carcinoma Cells by Inhibiting DNMT1 Expression.Frontiers in pharmacology · 2020Article
- Alterations of regulatory factors and DNA methylation pattern in thyroid cancer.Cancer biomarkers : section A of Disease markers · 2020Article
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- Glucose Metabolism on Tumor Plasticity, Diagnosis, and Treatment.Frontiers in oncology · 2020Review
- Epigenetic Gene Regulation by Dietary Compounds in Cancer Prevention.Advances in nutrition (Bethesda, Md.) · 2019Article
- Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells.Cell death & disease · 2019Article
- Role of ten-eleven translocation proteins and 5-hydroxymethylcytosine in hepatocellular carcinoma.Cell proliferation · 2019Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background5-Azacytidine (5-AZA), a DNA methyl transferase inhibitor, is a clinically used epigenetic drug for cancer therapy. Recently, we have shown that 5-AZA upregulates ten-eleven translocation (TET) protein expression in hepatocellular carcinoma (HCC) cells, which induce active demethylation. Vitamin C facilitates TET activity and enhances active demethylation. The aim of this study is to investigate whether vitamin C is able to enhance the effect of 5-AZA on active demethylation and to evaluate its consequence in HCC cell lines.
methodsHCC cell lines (Huh7 and HLE) were treated with 5-AZA and vitamin C. After 48 h of treatment, viability (resazurin conversion), toxicity (lactose dehydrogenase (LDH) release), and proliferation ((proliferating cell nuclear antigen (PCNA)) of single- and combined-treated cells were assessed. The effect of the treatment on 5-hydroxymethylcytosine (5hmC) intensity (immunofluorescence (IF) staining), TET, Snail, GADD45B, and P21 mRNA (real-time PCR) and protein expression (Western blot) were investigated.
resultsOur results indicated that vitamin C enhances the anti-proliferative and apoptotic effect of 5-AZA in HCC cell lines. By further analyzing the events leading to cell cycle arrest, we have shown for the first time in HCC that the combination of 5-AZA and vitamin C leads to an enhanced downregulation of Snail expression, a key transcription factor governing epithelial-mesenchymal transition (EMT) process, and cell cycle arrest.
conclusionsWe conclude that when combined with 5-AZA, vitamin C enhances TET activity in HCC cells, leading to induction of active demethylation. An increase in P21 expression as a consequence of downregulation of Snail accompanied by the induction of GADD45B expression is the main mechanism leading to cell cycle arrest in HCCs.
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