ArticleJournal of experimental & clinical cancer research : CR2017
Trifluoperazine, a novel autophagy inhibitor, increases radiosensitivity in glioblastoma by impairing homologous recombination.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.Clinical drug investigation · 2026Review
- Review
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- A bibliometric analysis of global research trends in autophagy and glioblastomas.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Death-ision: the link between cellular resilience and cancer resistance to treatments.Molecular cancer · 2025Review
- GDF15 Drives Glioblastoma Radioresistance by Inhibiting Ferroptosis and Remodeling the Immune Microenvironment.International journal of biological sciences · 2025Article
- The Pivotal Role of Irradiation-induced Autophagy Mechanisms in Glioma Therapy.Anti-cancer agents in medicinal chemistry · 2025Review
- Use of antipsychotic drugs during radiotherapy in adult cancer patients in Korea: a nationwide retrospective cohort study based on the national health insurance service database.Radiation oncology (London, England) · 2024Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Targeting the organelle for radiosensitization in cancer radiotherapy.Asian journal of pharmaceutical sciences · 2024Review
- Methotrimeprazine is a neuroprotective antiviral in JEV infection via adaptive ER stress and autophagy.EMBO molecular medicine · 2024Article
- The role of autophagy in hypoxia-induced radioresistance.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Review
- Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells.Frontiers in oncology · 2023Review
- Review
- Inhibiting Cytoprotective Autophagy in Cancer Therapy: An Update on Pharmacological Small-Molecule Compounds.Frontiers in pharmacology · 2022Review
- Repurposing Antipsychotics for Cancer Treatment.Biomedicines · 2021Review
- Callyspongiolide kills cells by inducing mitochondrial dysfunction via cellular iron depletion.Communications biology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResistance to adjuvant radiotherapy is a major cause of treatment failure in patients with glioblastoma (GBM). Autophagy inhibitors have been shown to enhance the efficacy of radiotherapy for certain solid tumors. However, current inhibitors do not penetrate the blood-brain-barrier (BBB). Here, we assessed the radiosensitivity effects of the antipsychotic drug trifluoperazine (TFP) on GBM in vitro and in vivo.
methodsU251 and U87 GBM cell lines as well as GBM cells from a primary human biopsy (P3), were used in vitro and in vivo to evaluate the efficacy of TFP treatment. Viability and cytotoxicity was evaluated by CCK-8 and clonogenic formation assays. Molecular studies using immunohistochemistry, western blots, immunofluorescence and qPCR were used to gain mechanistic insight into the biological activity of TFP. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models.
resultsIC50 values of U251, U87 and P3 cells treated with TFP were 16, 15 and 15.5 μM, respectively. TFP increased the expression of LC3B-II and p62, indicating a potential disruption of autophagy flux. These results were further substantiated by a decreased Lysotracker Red uptake, indicating impaired acidification of the lysosomes. We show that TFP and radiation had an additive effect when combined. This effect was in part due to impaired TFP-induced homologous recombination. Mechanistically we show that down-regulation of cathepsin L might explain the radiosensitivity effect of TFP. Finally, combining TFP and radiation resulted in a significant antitumor effect in orthotopic GBM xenograft models.
conclusionsThis study provides a strong rationale for further clinical studies exploring the combination therapy of TFP and radiation to treat GBM patients.
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