ArticleNature communications2023
The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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.
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Who cites it
64 citing papers in PubMed, 82 citations in OpenAlex.
- Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026Review
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- PLA2G2F suppresses ferroptosis through phospholipid remodeling.Nature structural & molecular biology · 2026Article
- Piezoelectric Nanozymes With Acoustically Rejuvenated Catalytic Activities Rewire Lipid Metabolism for Two-Pronged Ferroptotic Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- A comprehensive plasma-based approach to thromboinflammation in bladder cancer: integrating lipidomics, thrombin generation, and NETosis biomarkers.Journal of translational medicine · 2026Article
- A ferroptosis-suppressive state drives resistance to bladder-preserving chemoradiotherapy in muscle-invasive bladder cancer.Signal transduction and targeted therapy · 2026Article
- Construction and validation of a model based on necroptosis-related genes for predicting glioma prognosis.Discover oncology · 2026Article
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Host-specific platelet-activating factor acetylhydrolase selectively remodels diacylglycerophospholipids to control schistosome development.PLoS pathogens · 2026Article
- Lp-PLA2-derived LysoPC drives dendritic cell immunogenic activation and Th17 inflammation in severe asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis.Cell reports · 2026Article
- DGAT1 mediates sex-specific CD8Nature metabolism · 2026Article
- Pirin Transcriptionally Regulates PLA2G4A To Inhibit Ferroptosis in Colorectal Cancer via Lipid Profile Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Phospholipid Metabolism as an Effective Hearing Protection Strategy.Neuroscience bulletin · 2026Article
- Context-dependent Activities of Mitrephorone Link Lipid Redirection, Anti-inflammatory Action, and Ferroptosis Control to Hepatocyte Protection.Theranostics · 2026Article
- Oxidative stress as a nexus: Integrating mitophagy and ferroptosis in endometrial carcinogenesis (Review).Oncology letters · 2026Review
- Lipoprotein-associated phospholipase A2 (Lp-PLA2): a key hub linking lipid metabolism and immune inflammation.Frontiers in immunology · 2026Review
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Natural products targeting programmed cell death: a novel therapeutic strategy for intervertebral disc degeneration.International journal of surgery (London, England) · 2026Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.
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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.