ArticleOncotarget2017
Valproic acid inhibits glioblastoma multiforme cell growth via paraoxonase 2 expression.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Upregulation of paraoxonase-2 enzyme in human osteosarcoma and its involvement in mechanisms promoting the aggressive behavior of tumor cells.Molecular biology reports · 2026Article
- Paraoxonases as metabolic and signaling modulators: prospects for therapeutic and preventive implications.npj metabolic health and disease · 2026Review
- Spatial transcriptomics of glioblastoma defines biologically and clinically significant reprogramming patterns across unique spatial microenvironments.bioRxiv : the preprint server for biology · 2025Article
- Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells.Scientific reports · 2025Article
- Neural Vulnerabilities in Glioblastoma: Rethinking Therapy Through Neuroactive Drug Repurposing.Brain tumor research and treatment · 2025Review
- Role of paraoxonase 2 (PON2) as a potential biomarker and therapeutic target in cancer treatment.Journal of cancer research and clinical oncology · 2025Review
- Brain Tumor Related Epilepsy: Pathophysiology and Multimodal Approach to Management.Current oncology reports · 2025Review
- Effects of thymoquinone and the curcumin analog EF-24 on the activity of the enzyme paraoxonase-1 in human glioblastoma cells U87MG.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Contribution of the Paraoxonase-2 Enzyme to Cancer Cell Metabolism and Phenotypes.Biomolecules · 2024Review
- Regulation of Nrf2/Keap1 signaling pathway in cancer drug resistance by galectin-1: cellular and molecular implications.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.Frontiers in immunology · 2024Review
- Paraoxonase-2 is upregulated in triple negative breast cancer and contributes to tumor progression and chemoresistance.Human cell · 2023Article
- Paraoxonases at the Heart of Neurological Disorders.International journal of molecular sciences · 2023Review
- Integration of clinical and spatial data to explore lipid metabolism-related genes for predicting prognosis and immune microenvironment in gliomas.Functional & integrative genomics · 2023Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy.Life (Basel, Switzerland) · 2022Review
- Glioblastoma: Current Status, Emerging Targets, and Recent Advances.Journal of medicinal chemistry · 2022Review
- Insights into the role of paraoxonase 2 in human pathophysiology.Journal of biosciences · 2022Article
- Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment.Cancers · 2021Review
- Valproic Acid Sensitizes Glioma Cells to Luteolin Through Induction of Apoptosis and Autophagy via Akt Signaling.Cellular and molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied the potential mechanisms of valproic acid (VPA) in the treatment of glioblastoma multiforme (GBM). Using the human U87, GBM8401, and DBTRG-05MG GBM-derived cell lines, VPA at concentrations of 5 to 20 mM induced G2/M cell cycle arrest and increased the production of reactive oxygen species (ROS). Stress-related molecules such as paraoxonase 2 (PON2), cyclin B1, cdc2, and Bcl-xL were downregulated, but p27, p21 and Bim were upregulated by VPA treatment. VPA response element on the PON2 promoter was localized at position -400/-1. PON2 protein expression was increased in GBM cells compared with normal brain tissue and there was a negative correlation between the expression of PON2 and Bim. These findings were confirmed by the public Bredel GBM microarray (Gene Expression Omnibus accession: GSE2223) and the Cancer Genome Atlas GBM microarray datasets. Overexpression of PON2 in GBM cells significantly decreased intracellular ROS levels, and PON2 expression was decreased after VPA stimulation compared with controls. Bim expression was significantly induced by VPA in GBM cells with PON2 silencing. These observations were further shown in the subcutaneous GBM8401 cell xenograft of BALB/c nude mice. Our results suggest that VPA reduces PON2 expression in GBM cells, which in turn increases ROS production and induces Bim production that inhibits cancer progression via the PON2-Bim cascade.
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Registered trials
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