ArticlePloS one2014
PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 42 citations in OpenAlex.
- Olaparib: A Chemosensitizer for the Treatment of Glioblastoma.Mini reviews in medicinal chemistry · 2025Review
- Unite and Conquer: Association of Two G-Quadruplex Aptamers Provides Antiproliferative and Antimigration Activity for Cells from High-Grade Glioma Patients.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Investigating the Effects of Olaparib on the Susceptibility of Glioblastoma Multiforme Tumour Cells to Natural Killer Cell-Mediated Responses.Pharmaceutics · 2023Article
- Article
- BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort.Oncology · 2021Article
- Accurately Controlled Delivery of Temozolomide by Biocompatible UiO-66-NHInternational journal of nanomedicine · 2021Article
- ONC201 and imipridones: Anti-cancer compounds with clinical efficacy.Neoplasia (New York, N.Y.) · 2020Review
- The Modified Phenanthridine PJ34 Unveils an Exclusive Cell-Death Mechanism in Human Cancer Cells.Cancers · 2020Review
- Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma.British journal of cancer · 2020Article
- Current clinical management of patients with glioblastoma.Cancer reports (Hoboken, N.J.) · 2019Review
- Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events.Cancers · 2019Article
- Bcl-2/Bcl-xL inhibition predominantly synergistically enhances the anti-neoplastic activity of a low-dose CUSP9 repurposed drug regime against glioblastoma.British journal of pharmacology · 2019Article
- Combined inhibition of RAC1 and Bcl-2/Bcl-xL synergistically induces glioblastoma cell death through down-regulation of the Usp9X/Mcl-1 axis.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Targeting Cancer Stem Cells to Overcome Chemoresistance.International journal of molecular sciences · 2018Review
- Metabolic Reprogramming by Dual AKT/ERK Inhibition through Imipridones Elicits Unique Vulnerabilities in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Dual Inhibition of Bcl-2/Bcl-xL and XPO1 is synthetically lethal in glioblastoma model systems.Scientific reports · 2018Article
- Inhibition of Bcl-2/Bcl-xL and c-MET causes synthetic lethality in model systems of glioblastoma.Scientific reports · 2018Article
- A small compound spindlactone A sensitizes human endometrial cancer cells to TRAIL-induced apoptosis via the inhibition of NAD(P)H dehydrogenase quinone 1.OncoTargets and therapy · 2018Article
- Anti-glioma Activity of Dapsone and Its Enhancement by Synthetic Chemical Modification.Neurochemical research · 2017Article
- Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL.Nature communications · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundResistance to apoptosis is a paramount issue in the treatment of Glioblastoma (GBM). We show that targeting PARP by the small molecule inhibitors, Olaparib (AZD-2281) or PJ34, reduces proliferation and lowers the apoptotic threshold of GBM cells in vitro and in vivo.
methodsThe sensitizing effects of PARP inhibition on TRAIL-mediated apoptosis and potential toxicity were analyzed using viability assays and flow cytometry in established GBM cell lines, low-passage neurospheres and astrocytes in vitro. Molecular analyses included western blots and gene silencing. In vivo, effects on tumor growth were examined in a murine subcutaneous xenograft model.
resultsThe combination treatment of PARP inhibitors and TRAIL led to an increased cell death with activation of caspases and inhibition of formation of neurospheres when compared to single-agent treatment. Mechanistically, pharmacological PARP inhibition elicited a nuclear stress response with up-regulation of down-stream DNA-stress response proteins, e.g., CCAAT enhancer binding protein (C/EBP) homology protein (CHOP). Furthermore, Olaparib and PJ34 increased protein levels of DR5 in a concentration and time-dependent manner. In turn, siRNA-mediated suppression of DR5 mitigated the effects of TRAIL/PARP inhibitor-mediated apoptosis. In addition, suppression of PARP-1 levels enhanced TRAIL-mediated apoptosis in malignant glioma cells. Treatment of human astrocytes with the combination of TRAIL/PARP inhibitors did not cause toxicity. Finally, the combination treatment of TRAIL and PJ34 significantly reduced tumor growth in vivo when compared to treatment with each agent alone.
conclusionsPARP inhibition represents a promising avenue to overcome apoptotic resistance in GBM.
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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.