ArticleCell death & disease2025
Monounsaturated fatty acids promote cancer radioresistance by inhibiting ferroptosis through ACSL3.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- SIRT7-mediated ACSL3 delactylation suppresses colorectal cancer progression by orchestrating tumor-associated macrophage ferroptosis and polarization.Cell death & disease · 2026Article
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Review
- Multiomic and functional validation of ACSL3, a regulator of fatty acid metabolism, as a lymph node metastasis-associated gene in lung adenocarcinoma.Respiratory research · 2026Article
- Ferroptosis: The Demise of Cells Through Phospholipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Pan-Cancer profiling of ferroptosis-related genes reveals prognostic biomarkers and sex-specific associations.Clinical and translational radiation oncology · 2026Article
- Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3.Acta pharmaceutica Sinica. B · 2026Article
- Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.Antioxidants (Basel, Switzerland) · 2026Review
- Context-dependent Activities of Mitrephorone Link Lipid Redirection, Anti-inflammatory Action, and Ferroptosis Control to Hepatocyte Protection.Theranostics · 2026Article
- Review
- Oleic Acid Improves Goat Sperm Quality by Enhancing the MBOAT2/ACSL3 Pathway to Attenuate Ferroptosis.Animals : an open access journal from MDPI · 2025Article
- Multidimensional analysis reveals the potential of ACSL3 as a cancer biomarker: from pan-cancer exploration to functional validation in hepatocellular carcinoma.Clinical and experimental medicine · 2025Article
- Plin4 modulates lipid droplet accumulation and ferroptosis in neurons exposed to benzo[a]pyrene.Cell death discovery · 2025Article
- miR-4537 curtails ferroptosis by targeting MIOX in renal cell carcinoma.Translational oncology · 2025Article
- Molecular Insights into Oxidative-Stress-Mediated Cardiomyopathy and Potential Therapeutic Strategies.Biomolecules · 2025Review
- Mechanistic pathways predictive modeling and translational interventions for radiation enteritis in cervical cancer radiotherapy.Frontiers in cellular and infection microbiology · 2025Review
- Commentary: Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.Frontiers in pharmacology · 2025Article
- Ferroptosis: a double-edged sword that enhances radiation sensitivity and facilitates radiation-induced injury in tumors.Frontiers in immunology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors.
Funding
Abstract
Radioresistance is a major challenge in tumor radiotherapy and involves in a mixture of cellular events, including ferroptosis, a new type of programmed cell death characterized by the excess accumulation of iron-dependent lipid peroxides. In the present study, we observed that surviving cancer tissues and cells after radiotherapy had significantly greater glutathione to oxidized glutathione (GSH/GSSG) ratios and lower lipid reactive oxygen species (ROS) and malondialdehyde (MDA) levels than nonirradiated tumors and cells. Untargeted lipidomic analyses revealed that oleic acid (OA) and palmitoleic acid (POA) were the most significantly upregulated unsaturated fatty acids in irradiated surviving cancer cells compared with those in control cancer cells irradiated with IR. Both OA and POA could protect cancer cells from the killing effects of the ferroptosis inducer erastin and RSL3, and OA had a stronger protective effect than POA, resulting in lower lipid ROS production than POA. Mechanistically, OA protected cells from ferroptosis caused by the accumulation of polyunsaturated fatty acid-containing phospholipids in an ACSL3-dependent manner. A mouse model demonstrated that ACSL3 knockdown combined with imidazole ketone erastin synergistically enhanced antitumor effects in radiation-resistant tumors in vivo. Our study reveals previously undiscovered associations between radiation and fatty acid metabolism and ferroptosis, providing a novel treatment strategy for overcoming cancer radioresistance.
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