ArticleInternational journal of molecular sciences2019
Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Application of HepG2-derived organoid and organ-on-a-chip platforms in elucidating selenium-mediated protection against cadmium-induced liver dysfunction.NPJ science of food · 2026Article
- Mechanistic Insights into Hepatic Pathogenesis of Dengue Virus Serotype-2: Host-Virus Interactions, Immune Dysregulation, and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening.Archives of toxicology · 2025Article
- Review
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- Antiretrovirals Promote Metabolic Syndrome through Mitochondrial Stress and Dysfunction: An In Vitro Study.Biology · 2023Article
- Article
- Antiretrovirals Promote Insulin Resistance in HepG2 Liver Cells through miRNA Regulation and Transcriptional Activation of the NLRP3 Inflammasome.International journal of molecular sciences · 2023Article
- Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids.Scientific reports · 2023Article
- DNMT1/PKR double knockdowned HepG2 (HepG2-DP) cells have high hepatic function and differentiation ability.Scientific reports · 2022Article
- Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.Stem cells international · 2022Article
- Review
- The Felicitous Success of the Subsection Molecular Oncology of International Journal of Molecular Sciences.International journal of molecular sciences · 2021Article
- Electrolyzed Hydrogen Water Protects against Ethanol-Induced Cytotoxicity by Regulating Aldehyde Metabolism-Associated Enzymes in the Hepatic Cell Line HepG2.Antioxidants (Basel, Switzerland) · 2021Article
- Elevated levels of expression of cytochrome P450 3A4 in a human liver epithelial cell line in differentiation-inducing conditions.Human cell · 2021Article
- Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications.Frontiers in bioengineering and biotechnology · 2021Review
- Application of In Vitro Metabolism Activation in High-Throughput Screening.International journal of molecular sciences · 2020Review
- DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver.GeroScience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards 'normal' liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.
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Registered trials
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