ArticleJournal of neuro-oncology2007
Valproic acid induces p21 and topoisomerase-II (alpha/beta) expression and synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines.
Article in Journal of neuro-oncology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06199557 (A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid), which is not on this map. Cited by 54 papers.
What it found
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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.
A Phase 1/2 Multicenter Open-label Study to Investigate Treatment of Hydroxyurea in Combination With Valproic Acid (VPA), or 6- Mercaptopurine in Combination With VPA in Patients With AML or HR-MDS Unfit for Standard Therapy
Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- Phase II study of sodium valproate in combination with oral etoposide in platinum-resistant ovarian cancer.Medical oncology (Northwood, London, England) · 2022Trial
- Valproic acid was well tolerated in heavily pretreated pediatric patients with high-grade glioma.Journal of neuro-oncology · 2008Trial
- The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.Frontiers in oncology · 2024Review
- Antitumor Potential of Antiepileptic Drugs in Human Glioblastoma: Pharmacological Targets and Clinical Benefits.Biomedicines · 2023Review
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Molecular pathways in glioblastoma-derived stem cells to identify effective drug agents: A bioinformatics study.Journal of family medicine and primary care · 2022Article
- Synergistic Effect of Simultaneous versus Sequential Combined Treatment of Histone Deacetylase Inhibitor Valproic Acid with Etoposide on Melanoma Cells.International journal of molecular sciences · 2021Article
- Review
- Cytotoxic Effects of Hellebrigenin and Arenobufagin Against Human Breast Cancer Cells.Frontiers in oncology · 2021Article
- Article
- Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death.International journal of molecular sciences · 2020Article
- The Anti-Tumorigenic Activity of Sema3C in the Chick Embryo Chorioallantoic Membrane Model.International journal of molecular sciences · 2019Article
- Emerging therapeutic potential of anti-psychotic drugs in the management of human glioma: A comprehensive review.Oncotarget · 2019Review
- Transcriptional repressor REST drives lineage stage-specific chromatin compaction atScience signaling · 2019Article
- Combination Therapy with Sulfasalazine and Valproic Acid Promotes Human Glioblastoma Cell Death Through Imbalance of the Intracellular Oxidative Response.Molecular neurobiology · 2018Article
- Pre-treatment or Post-treatment of Human Glioma Cells With BIX01294, the Inhibitor of Histone Methyltransferase G9a, Sensitizes Cells to Temozolomide.Frontiers in pharmacology · 2018Article
- Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.Frontiers in oncology · 2018Review
- Valproic acid inhibits glioblastoma multiforme cell growth via paraoxonase 2 expression.Oncotarget · 2017Article
- Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma.PloS one · 2017Article
- Valproic acid inhibits the angiogenic potential of cervical cancer cells via HIF-1α/VEGF signals.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectEtoposide, a topoisomerase-II inhibitor promotes DNA damage and apoptosis of cancer cells. In this study, we have examined the ability of the histone deacetylase inhibitor, valproic acid (VPA) to modulate gene expression and sensitize glioblastoma cell lines to the cytotoxic effects of etoposide in vitro.
methodsThe effect of VPA and etoposide alone or a combination of the two drugs on the growth of three different glioblastoma cell lines (U87, LN18, and U251) were measured by MTT assays. Drug treated cells were analyzed for their cell cycle profile, gene expression, differentiation status, and induction of apoptosis by flow-cytometry, western blotting, immunofluorescence assays, and caspase activity measurements.
resultsWe observed that while VPA and etoposide independently inhibited the growth of U87, U251, and LN18 cells, exposure of tumor cells to both drugs significantly enhanced the cytotoxicity of etoposide in all cell lines. VPA promoted a G(1) accumulation of U87, while an increase in the G(2)/M population of U251 and LN18 cells was observed upon exposure to the drug. Treatment with etoposide resulted in a G(2)/M arrest of U87, U251, and LN18 cells, whereas, exposure to both drugs increased the fraction of cells with a G2/M and sub-G1 DNA content. Further, VPA and not etoposide, promoted acetylation of histone H4 and induced the expression of the cyclin-dependent kinase inhibitor (CDKI), p21/WAF1. VPA also up-regulated the expression of the alpha and beta isoforms of topoisomerase-II, as well as the glial differentiation marker, glial fibrillary acidic protein. Finally, a significant increase in caspase-3 activity and apoptosis was observed in the presence of both VPA and etoposide compared to either agent alone.
conclusionOur study demonstrates that VPA sensitizes U87, U251, and LN18 cells to the cytotoxic effects of etoposide in vitro by inducing differentiation and up-regulating the expression of p21/WAF1 and both isoforms of topoisomerase-II.
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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.