ArticlePloS one2013
Human glioblastoma multiforme: p53 reactivation by a novel MDM2 inhibitor.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Redox Regulation in Glioblastoma: Mechanisms, Biomarkers, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Dysfunction of the Autophagy System and MDM2-p53 Axis Leads to the Accumulation of Amyloidogenic Proteins in Angelman Syndrome Models.International journal of molecular sciences · 2025Article
- Exploring the therapeutic role of carnosol in cancer: from molecular insights to clinical promise.Medical oncology (Northwood, London, England) · 2025Review
- Glioblastoma Therapy: Past, Present and Future.International journal of molecular sciences · 2024Review
- Cellular senescence in glioma.Journal of neuro-oncology · 2023Review
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Target-Based Anticancer Indole Derivatives for the Development of Anti-Glioblastoma Agents.Molecules (Basel, Switzerland) · 2023Review
- Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold Repurposing Approach.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Post-Transcriptional Modifications of RNA as Regulators of Apoptosis in Glioblastoma.International journal of molecular sciences · 2022Review
- Mechanisms of Cell Cycle Arrest and Apoptosis in Glioblastoma.Biomedicines · 2022Review
- Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenicFrontiers in oncology · 2022Article
- AaTs-1: A Tetrapeptide fromMolecules (Basel, Switzerland) · 2021Article
- A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials.Cancers · 2021Review
- Oxidative Stress Activated by Sorafenib Alters the Temozolomide Sensitivity of Human Glioma Cells Through Autophagy and JAK2/STAT3-AIF Axis.Frontiers in cell and developmental biology · 2021Article
- MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.Frontiers in oncology · 2021Review
- Molecular Mechanisms of Treatment Resistance in Glioblastoma.International journal of molecular sciences · 2020Review
- Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance.Cancers · 2019Review
- Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells' Extracellular Vesicles.The Malaysian journal of medical sciences : MJMS · 2019Review
- Targeted Therapies for the Treatment of Glioblastoma in Adults.Current oncology reports · 2019Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer development and chemo-resistance are often due to impaired functioning of the p53 tumor suppressor through genetic mutation or sequestration by other proteins. In glioblastoma multiforme (GBM), p53 availability is frequently reduced because it binds to the Murine Double Minute-2 (MDM2) oncoprotein, which accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors that interfere with the binding of p53 and MDM2 has become a valid approach to inhibit cell growth in a number of cancers; however little is known about the efficacy of these inhibitors in GBM. We report that a new small-molecule inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27, effectively reactivated p53 function and inhibited human GBM cell growth in vitro by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated p53, inhibited cell proliferation and induced apoptosis in tumor tissue. Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ) produced a synergistic inhibitory effect on GBM cell viability in vitro, suggesting the possibility of lowering the dose of TMZ used in the treatment of GBM. In conclusion, our data show that ISA27 releases the powerful antitumor capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a novel therapy for the treatment of GBM patients.
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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.