ArticleScientific reports2017
Valproic Acid Sensitizes Hepatocellular Carcinoma Cells to Proton Therapy by Suppressing NRF2 Activation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 46 citations in OpenAlex.
- Simultaneous Inhibition of ACLY and OGDH Has a Synergistic Effect on Hepatocellular Carcinoma Cell Lines.bioRxiv : the preprint server for biology · 2026Article
- A Cisplatin-Based Prodrug Inhibits Nucleotide Excision Repair Independently of Chromatin Accessibility to Overcome Resistance.Biomolecules · 2026Article
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Mechanism and application of HDAC inhibitors in the treatment of hepatocellular carcinoma.Journal of molecular medicine (Berlin, Germany) · 2025Review
- NRG Oncology White Paper on the Relative Biological Effectiveness in Proton Therapy.International journal of radiation oncology, biology, physics · 2025Review
- HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair.Cancers · 2024Article
- Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast Cell Line.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanistic Sequence of Histone Deacetylase Inhibitors and Radiation Treatment: An Overview.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Valproic Acid Causes Redox-Regulated Post-Translational Protein Modifications That Are Dependent upon P19 Cellular Differentiation States.Antioxidants (Basel, Switzerland) · 2024Article
- Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model.International journal of molecular sciences · 2023Article
- Control of Redox Homeostasis by Short-Chain Fatty Acids: Implications for the Prevention and Treatment of Breast Cancer.Pathogens (Basel, Switzerland) · 2023Review
- Immunomodulation of HDAC Inhibitor Entinostat Potentiates the Anticancer Effects of Radiation and PD-1 Blockade in the Murine Lewis Lung Carcinoma Model.International journal of molecular sciences · 2022Article
- Valproic acid disables the Nrf2 anti-oxidant response in acute myeloid leukaemia cells enhancing reactive oxygen species-mediated killing.British journal of cancer · 2022Article
- High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations.International journal of molecular sciences · 2022Article
- Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.Cellular and molecular life sciences : CMLS · 2021Review
- A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond.Journal of personalized medicine · 2021Review
- Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.Journal of personalized medicine · 2021Review
- Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells.Cells · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although efficacy of combined histone deacetylase (HDAC) inhibitors and conventional photon radiotherapy is being tested in clinical trials, their combined effect with proton beam radiotherapy has yet to be determined. Here, we compared combined effect of valproic acid (VPA), a class I and II HDAC inhibitor and antiepileptic drug with proton and photon irradiation in hepatocellular carcinoma (HCC) cells in vitro and in vivo. We found that VPA sensitized more Hep3B cells to proton than to photon irradiation. VPA prolonged proton-induced DNA damage and augmented proton-induced apoptosis. In addition, VPA further increased proton-induced production of intracellular reactive oxygen species and suppressed expression of nuclear factor erythroid-2-related factor 2 (NRF2), a key transcription factor regulating antioxidant response. Downregulation of NRF2 by siRNA transfection increased proton-induced apoptotic cell death, supporting NRF2 as a target of VPA in radiosensitization. In Hep3B tumor xenograft models, VPA significantly enhanced proton-induced tumor growth delay with increased apoptosis and decreased NRF2 expression in vivo. Collectively, our study highlights a proton radiosensitizing effect of VPA in HCC cells. As NRF2 is an emerging prognostic marker contributing to radioresistance in HCC, targeting NRF2 pathway may impact clinical outcome of proton beam radiotherapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.