ArticleOncotarget2015
The peroxisome proliferator activated receptor gamma agonist pioglitazone increases functional expression of the glutamate transporter excitatory amino acid transporter 2 (EAAT2) in human 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 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Tumor-associated epilepsy and high expression of xCT shape the proteome of IDH-wildtype glioblastoma.Cell death discovery · 2026Article
- The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation.Neurochemical research · 2026Article
- Disrupted glutamate homeostasis as a target for glioma therapy.Pharmacological reports : PR · 2024Review
- Exploring the molecular mechanisms of PPARγ agonists in modulating memory impairment in neurodegenerative disorders.Molecular biology reports · 2024Review
- Repurposed Drugs Celecoxib and Fmoc-L-Leucine Alone and in Combination as Temozolomide-Resistant Antiglioma Agents-Comparative Studies on Normal and Immortalized Cell Lines, and onInternational journal of molecular sciences · 2024Article
- Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.Frontiers in oncology · 2023Review
- The Use of Photodynamic Therapy in the Treatment of Brain Tumors-A Review of the Literature.Molecules (Basel, Switzerland) · 2022Review
- Review
- Treatment of acromegaly by rosiglitazone via upregulating 15-PGDH in both pituitary adenoma and liver.iScience · 2021Article
- Adenosine Receptor A1-A2a Heteromers Regulate EAAT2 Expression and Glutamate Uptake via YY1-Induced Repression of PPARPPAR research · 2020Article
- Safety of pioglitazone during and after radiation therapy in patients with brain tumors: a phase I clinical trial.Journal of cancer research and clinical oncology · 2019Article
- Pioglitazone use in patients with diabetes and risk of bladder cancer: a systematic review and meta-analysis.Cancer management and research · 2018Review
- Peroxisome proliferator-activated receptor-gamma: potential molecular therapeutic target for HIV-1-associated brain inflammation.Journal of neuroinflammation · 2017Article
- Metabotropic glutamate receptor 5 may be involved in macrophage plasticity.Biological research · 2017Article
- Metabolic Reprogramming in Glioma.Frontiers in cell and developmental biology · 2017Review
- Pituitary Adenylate cyclase-activating polypeptide orchestrates neuronal regulation of the astrocytic glutamate-releasing mechanism system xc (.).Journal of neurochemistry · 2016Article
- Seizures and gliomas--towards a single therapeutic approach.Nature reviews. Neurology · 2016Review
- Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair.Progress in neurobiologyReview
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioma cells release glutamate through expression of system xc-, which exchanges intracellular glutamate for extracellular cysteine. Lack of the excitatory amino acid transporter 2 (EAAT2) expression maintains high extracellular glutamate levels in the glioma microenvironment, causing excitotoxicity to surrounding parenchyma. Not only does this contribute to the survival and proliferation of glioma cells, but is involved in the pathophysiology of tumour-associated epilepsy (TAE). We investigated the role of the peroxisome proliferator activated receptor gamma (PPARγ) agonist pioglitazone in modulating EAAT2 expression in glioma cells. We found that EAAT2 expression was increased in a dose dependent manner in both U87MG and U251MG glioma cells. Extracellular glutamate levels were reduced with the addition of pioglitazone, where statistical significance was reached in both U87MG and U251MG cells at a concentration of ≥ 30 μM pioglitazone (p < 0.05). The PPARγ antagonist GW9662 inhibited the effect of pioglitazone on extracellular glutamate levels, indicating PPARγ dependence. In addition, pioglitazone significantly reduced cell viability of U87MG and U251MG cells at ≥ 30 μM and 100 μM (p < 0.05) respectively. GW9662 also significantly reduced viability of U87MG and U251MG cells with 10 μM and 30 μM (p < 0.05) respectively. The effect on viability was partially dependent on PPARγ activation in U87MG cells but not U251MG cells, whereby PPARγ blockade with GW9662 had a synergistic effect. We conclude that PPARγ agonists may be therapeutically beneficial in the treatment of gliomas and furthermore suggest a novel role for these agents in the treatment of tumour associated seizures through the reduction in extracellular glutamate.
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