ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2024
Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Targeting ADAR1 in Cancer: Biology, Therapeutic Strategies, Challenges, and Limitations.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Single-cell evidence for PANoptosome complexes.Nature reviews. Molecular cell biology · 2026Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025Review
- PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations.Cellular & molecular immunology · 2025Review
- Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.Acta pharmacologica Sinica · 2025Article
- Microglia and programmed cell death in spinal cord injury: beyond apoptosis.Frontiers in cell and developmental biology · 2025Review
- Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilization in macrophages.Frontiers in immunology · 2025Article
- PANoptosis in urological diseases: molecular mechanisms, pathological roles, and emerging therapeutic opportunities.Frontiers in immunology · 2025Review
- Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making.Scientific reports · 2024Article
- Cell death shapes cancer immunity: spotlighting PANoptosis.Journal of experimental & clinical cancer research : CR · 2024Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectivePANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts. This study aimed to explore whether CBL0137 induces PANoptosis in macrophages in vitro and in mouse tissues in vivo.
methodsBone marrow-derived macrophages and J774A.1 cells were treated with CBL0137 or its combination with LPS for indicated time periods. Cell death was assayed by propidium iodide staining and immunoblotting. Immunofluorescence microscopy was used to detect cellular protein distribution. Mice were administered with CBL0137 plus LPS and their serum and tissues were collected for biochemical and histopathological analyses, respectively.
resultsThe results showed that CBL0137 alone or in combination with LPS induced time- and dose-dependent cell death in macrophages, which was inhibited by a combination of multiple forms of cell death inhibitors but not each alone. This cell death was independent of NLRP3 expression. CBL0137 or CBL0137 + LPS-induced cell death was characterized by simultaneously increased hallmarks for pyroptosis, apoptosis and necroptosis, indicating that this is PANoptosis. Induction of PANoptosis was associated with Z-DNA formation in the nucleus and likely assembly of PANoptosome. ZBP1 was critical in mediating CBL0137 + LPS-induced cell death likely by sensing Z-DNA. Moreover, intraperitoneal administration of CBL0137 plus LPS induced systemic inflammatory responses and caused multi-organ (including the liver, kidney and lung) injury in mice due to induction of PANoptosis in these organs.
conclusionsCBL0137 alone or plus inflammatory stimulation induces PANoptosis both in vitro and in vivo, which is associated with systemic inflammatory responses in mice.
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