ArticleOncotarget2015
Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- Exploiting Methyl Triazenes as Attractive Alternatives to Temozolomide and Dacarbazine for Cancer Therapy.Molecules (Basel, Switzerland) · 2026Review
- Persons with epilepsy have an elevated radiosensitivity, which may be mitigated by folic acid.Journal of neurology · 2026Article
- Potential neuroprotective and therapeutic agents and their mechanisms for irradiation-induced brain injury.Ibrain · 2026Review
- Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells.Scientific reports · 2025Article
- Research progress in glioma-related epilepsy (Review).Biomedical reports · 2025Article
- Isoliquiritigenin as a Neuronal Radiation Mitigant: Mitigating Radiation-Induced Anhedonia Tendency Targeting Grik3/Grm8/Grin3a via Integrated Proteomics and AI-Driven Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Brain Tumor Related Epilepsy: Pathophysiology and Multimodal Approach to Management.Current oncology reports · 2025Review
- In Vivo and In Vitro Experimental Study Comparing the Effect of a Combination of Sodium Dichloroacetate and Valproic Acid with That of Temozolomide on Adult Glioblastoma.International journal of molecular sciences · 2025Article
- Piperidine and valproic acid hybrid compound (F2S4-RSC advances · 2025Article
- Levetiracetam and valproic acid in glioma: antiseizure and potential antineoplastic effects.Future oncology (London, England) · 2025Review
- Differential Impact of Valproic Acid onBiomedicines · 2024Article
- Optimization, Characterization, and Comparison of Two Luciferase-Expressing Mouse Glioblastoma Models.Cancers · 2024Article
- Article
- Valproic acid as a radio-sensitizer in glioma: A systematic review and meta-analysis.Neuro-oncology practice · 2023Article
- Brief report: pediatric high-grade gliomas treated with vinorelbine and valproic acid added to temozolomide.American journal of cancer research · 2023Article
- A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells.Cell proliferation · 2023Article
- The effect of anticonvulsants on survival among patients with GBM brain tumors undergoing radiation: A SEER-Medicare analysis.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2022Article
- Neuroprotective agents effective against radiation damage of central nervous system.Neural regeneration research · 2022Review
- Valproic Acid Regulates HR and Cell Cycle Through MUS81-pRPA2 Pathway in Response to Hydroxyurea.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neurocognitive deficits are serious sequelae that follow cranial irradiation used to treat patients with medulloblastoma and other brain neoplasms. Cranial irradiation causes apoptosis in the subgranular zone of the hippocampus leading to cognitive deficits. Valproic acid (VPA) treatment protected hippocampal neurons from radiation-induced damage in both cell culture and animal models. Radioprotection was observed in VPA-treated neuronal cells compared to cells treated with radiation alone. This protection is specific to normal neuronal cells and did not extend to cancer cells. In fact, VPA acted as a radiosensitizer in brain cancer cells. VPA treatment induced cell cycle arrest in cancer cells but not in normal neuronal cells. The level of anti-apoptotic protein Bcl-2 was increased and the pro-apoptotic protein Bax was reduced in VPA treated normal cells. VPA inhibited the activities of histone deacetylase (HDAC) and glycogen synthase kinase-3β (GSK3β), the latter of which is only inhibited in normal cells. The combination of VPA and radiation was most effective in inhibiting tumor growth in heterotopic brain tumor models. An intracranial orthotopic glioma tumor model was used to evaluate tumor growth by using dynamic contrast-enhanced magnetic resonance (DCE MRI) and mouse survival following treatment with VPA and radiation. VPA, in combination with radiation, significantly delayed tumor growth and improved mouse survival. Overall, VPA protects normal hippocampal neurons and not cancer cells from radiation-induced cytotoxicity both in vitro and in vivo. VPA treatment has the potential for attenuating neurocognitive deficits associated with cranial irradiation while enhancing the efficiency of glioma radiotherapy.
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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.