ArticleCell death & disease2014
Celastrol targets proteostasis and acts synergistically with a heat-shock protein 90 inhibitor to kill human glioblastoma cells.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG).International journal of molecular sciences · 2022Pooled it
- Integrated bioinformatics analyses and cell line experiments implicate miR-33a-5p/HIF1A in the cellular response to celastrol in lung adenocarcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Tuning the Fire: Context-Dependent Mitochondrial ROS Signaling, Mitohormesis, and Redox-Modulating Interventions.Biomolecules · 2026Review
- Review
- Characterization of global research trends and prospects on celastrol, a principal bioactive ingredient ofPharmaceutical biology · 2025Article
- Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.Pediatric research · 2024Article
- Exploring the combined anti-cancer effects of sodium butyrate and celastrol in glioblastoma cell lines: a novel therapeutic approach.Medical oncology (Northwood, London, England) · 2024Article
- SoloxoloneFrontiers in pharmacology · 2024Article
- Recent Trends in anti-tumor mechanisms and molecular targets of celastrol.International journal of biological sciences · 2024Review
- Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023Review
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- Autophagy in the pharmacological activities of celastrol (Review).Experimental and therapeutic medicine · 2023Review
- Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.Metabolites · 2022Review
- Modulation of Inflammation-Related Lipid Mediator Pathways by Celastrol During Human Macrophage Polarization.Journal of inflammation research · 2022Article
- Regulation of autophagy as a therapeutic option in glioblastoma.Apoptosis : an international journal on programmed cell death · 2021Review
- Targeting Drug Chemo-Resistance in Cancer Using Natural Products.Biomedicines · 2021Review
- Celastrol exerts a neuroprotective effect by directly binding to HMGB1 protein in cerebral ischemia-reperfusion.Journal of neuroinflammation · 2021Article
- Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.International journal of nanomedicine · 2021Review
- Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots ofInternational journal of molecular sciences · 2020Article
- Article
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4 authors at 2 institutions in 1 country.
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Abstract
Glioblastoma multiforme is a devastating disease of the central nervous system and, at present, no effective therapeutic interventions have been identified. Celastrol, a natural occurring triterpene, exhibits potent anti-tumor activity against gliomas in xenograft mouse models. In this study, we describe the cell death mechanism employed by celastrol and identify secondary targets for effective combination therapy against glioblastoma cell survival. In contrast to the previously proposed reactive oxygen species (ROS)-dependent mechanism, cell death in human glioblastoma cells is shown here to be mediated by alternate signal transduction pathways involving, but not fully dependent on, poly(ADP-ribose) polymerase-1 and caspase-3. Our studies indicate that celastrol promotes proteotoxic stress, supported by two feedback mechanisms: (i) impairment of protein quality control as revealed by accumulation of polyubiquitinated aggregates and the canonical autophagy substrate, p62, and (ii) the induction of heat-shock proteins, HSP72 and HSP90. The Michael adduct of celastrol and N-acetylcysteine, 6-N-acetylcysteinyldihydrocelastrol, had no effect on p62, nor on HSP72 expression, confirming a thiol-dependent mechanism. Restriction of protein folding stress with cycloheximide was protective, while combination with autophagy inhibitors did not sensitize cells to celastrol-mediated cytotoxicity. Collectively, these findings imply that celastrol targets proteostasis by disrupting sulfyhydryl homeostasis, independently of ROS, in human glioblastoma cells. This study further emphasizes that targeting proteotoxic stress responses by inhibiting HSP90 with 17-N-Allylamino-17-demethoxygeldanamycin sensitizes human glioblastoma to celastrol treatment, thereby serving as a novel synergism to overcome drug resistance.
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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.