ArticleCell death & disease2017
Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation.Frontiers in oncology · 2025Article
- The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.CNS neuroscience & therapeutics · 2024Review
- Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.International journal of molecular sciences · 2024Review
- Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease.International journal of molecular sciences · 2024Review
- Targeting paraptosis in cancer: opportunities and challenges.Cancer gene therapy · 2024Review
- TNFRSF19 promotes endoplasmic reticulum stress-induced paraptosis via the activation of the MAPK pathway in triple-negative breast cancer cells.Cancer gene therapy · 2024Article
- Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.Frontiers in immunology · 2024Review
- A Mulberry Diels-Alder-Type Adduct, Kuwanon M, Triggers Apoptosis and Paraptosis of Lung Cancer Cells through Inducing Endoplasmic Reticulum Stress.International journal of molecular sciences · 2023Article
- Disulfiram Oxy-Derivatives Suppress Protein Retrotranslocation across the ER Membrane to the Cytosol and Initiate Paraptosis-like Cell Death.Membranes · 2022Article
- Review
- Significantly high expression of NUP37 leads to poor prognosis of glioma patients by promoting the proliferation of glioma cells.Cancer medicine · 2021Article
- Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation.Apoptosis : an international journal on programmed cell death · 2021Article
- Paraptosis and Photodynamic Therapy: A Progress Report.Photochemistry and photobiology · 2020Article
- Induced pluripotent stem cells as a novel cancer vaccine.Expert opinion on biological therapy · 2019Review
- Biological Actions of the Hsp90-binding Immunophilins FKBP51 and FKBP52Biomolecules · 2019Review
- Apoptosis, Paraptosis and Autophagy: Death and Survival Pathways Associated with Photodynamic Therapy.Photochemistry and photobiology · 2019Review
- The thiosemicarbazone MeCell death & disease · 2018Article
- The Multiple Roles of Peptidyl Prolyl Isomerases in Brain Cancer.Biomolecules · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality. We report that NIM811, a small molecule cyclophilin-binding inhibitor, induces catastrophic vacuolization and cell death in GBM cells. These unique features are distinct from many known cell death pathways, and are associated with an incompletely defined cell death mechanism known as paraptosis. We found that NIM811-induced paraptosis is due to unresolved ER stress. The abnormal upregulation of protein translation was responsible for the build-up of misfolded or unfolded proteins in ER, whereas pro-survival autophagy and UPR signals were shutdown during prolonged treatment with NIM811. Although cycloheximide has been claimed to suppress paraptosis, instead we find that it only temporarily delayed vacuole formation, but actually enhanced paraptotic cell death in the long term. On the other hand, mTOR inhibitors rescued cells from NIM811-induced paraptosis by sustaining autophagy and the UPR, while specifically restraining cap-dependent translation. These findings not only provide new insights into the mechanisms underlying paraptosis, but also shed light on a potential approach to enhance GBM treatment.
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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.