ArticleBritish journal of pharmacology2006
The antiepileptic and anticancer agent, valproic acid, induces P-glycoprotein in human tumour cell lines and in rat liver.
Article in British journal of pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- A Systematic Review and Classification of the Effects of P-glycoprotein Inhibitors and Inducers in Humans, Using Digoxin, Fexofenadine, and Dabigatran as Probe Drugs.Clinical pharmacokinetics · 2025Pooled it
- Antiseizure Medications in Older Adults with Epilepsy: Considerations in Pharmacology, Safety, Tolerability, and Effectiveness of Newer Agents.Drugs & aging · 2026Review
- Valproic Acid as a Histone Deacetylase Inhibitor InducesCurrent issues in molecular biology · 2025Article
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells.Molecular biology reports · 2024Article
- Structure-Function Relationships in the Human P-Glycoprotein (ABCB1): Insights from Molecular Dynamics Simulations.International journal of molecular sciences · 2021Article
- Association Between Use of Pharmacokinetic-Interacting Drugs and Effectiveness and Safety of Direct Acting Oral Anticoagulants: Nested Case-Control Study.Clinical pharmacology and therapeutics · 2021Article
- Effect of sodium butyrate on ABC transporters in lung cancer A549 and colorectal cancer HCT116 cells.Oncology letters · 2020Article
- Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban.Pharmaceutics · 2020Article
- Natural HDAC-1/8 inhibitor baicalein exerts therapeutic effect in CBF-AML.Clinical and translational medicine · 2020Article
- Edoxaban and the Issue of Drug-Drug Interactions: From Pharmacology to Clinical Practice.Drugs · 2020Review
- Homology Modeling of the Human P-glycoprotein (ABCB1) and Insights into Ligand Binding through Molecular Docking Studies.International journal of molecular sciences · 2020Article
- Epigenetic Regulation of Multidrug Resistance Protein 1 and Breast Cancer Resistance Protein Transporters by Histone Deacetylase Inhibition.Drug metabolism and disposition: the biological fate of chemicals · 2020Review
- Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study.Frontiers in neurology · 2020Article
- The Selective Class IIa Histone Deacetylase Inhibitor TMP195 Resensitizes ABCB1- and ABCG2-Overexpressing Multidrug-Resistant Cancer Cells to Cytotoxic Anticancer Drugs.International journal of molecular sciences · 2019Article
- Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs.Frontiers in neurology · 2018Review
- Effects of Valproic Acid on Cerebral Nutrient Carriers' Expression in the Rat.Frontiers in pharmacology · 2018Article
- In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2.Molecules (Basel, Switzerland) · 2017Article
- Breaking Bad: the Structure and Function of the Blood-Brain Barrier in Epilepsy.The AAPS journal · 2017Review
- Effective Drug Delivery in Diffuse Intrinsic Pontine Glioma: A Theoretical Model to Identify Potential Candidates.Frontiers in oncology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeThe antiepileptic drug valproic acid, a histone deacetylase (HDAC) inhibitor, is currently being tested as an anticancer agent. However, HDAC inhibitors may interact with anticancer drugs through induction of P-glycoprotein (P-gp, MDR1) expression. In this study we assessed whether valproic acid induces P-gp function in tumour cells. We also investigated effects of valproic acid on the mRNA for P-gp and the cytochrome P450, CYP3A, in rat livers. EXPERIMENTAL APPROACH: Effects of valproic acid on P-gp were assessed in three tumour cell lines, SW620, KG1a and H4IIE. Accumulation of acetylated histone H3 in rats' livers treated for two or seven days with valproic acid was evaluated using a specific antibody. Hepatic expression of the P-gp genes, mdr1a, mdr1b and mdr2, was determined by real-time polymerase chain reaction. The effects of valproic acid on CYP3A were assessed by Northern blot analysis and CYP3A activity assays. KEY
resultsValproic acid (0.5-2.0 mM) induced P-gp expression and function up to 4-fold in vitro. The effect of a series of valproic acid derivatives on P-gp expression in SW620 and KG1a cells correlated with their HDAC inhibition potencies. Treatment of rats with 1 mmol kg(-1) valproic acid for two and seven days increased hepatic histone acetylation (1.3- and 3.5-fold, respectively) and the expression of mdr1a and mdr2 (2.2-4.1-fold). Valpromide (0.5-2.0 mM) did not increase histone acetylation or P-gp expression in rat livers, but induced CYP3A expression.
conclusionsValproic acid increased P-gp expression and function in human tumour cell lines and in rat liver. The clinical significance of this increase merits further investigation.
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Registered trials
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