ArticleEuropean journal of nutrition2022
Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells.
Article in European journal of nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 51 citations in OpenAlex.
- Dystrophin Deficiency Creates a Pro-Ferroptotic Environment in Diaphragm of mdx Mice That Is Modified by Diet and Glucocorticoid Treatment.Biomolecules · 2026Article
- Docosahexaenoic Acid Enhances the Cytotoxic Effects of Enzalutamide and the PARP Inhibitor in Castration-Resistant Prostate Cancer Cell Lines.International journal of molecular sciences · 2026Article
- Integrated transcriptomic and in silico structural analysis identifies NFS1 and HSPA9 as potential regulators associated with mitochondrial ferroptosis and cell death resistance in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Dual activation of NLRP3 and pyrin inflammasomes mediates host responses to the human fungal pathogen Coccidioides.Nature communications · 2026Article
- Machine learning-based multi-omic analysis identifies CEP55, DLGAP5, and EZH2 as regulated cell death biomarkers linked to immunotherapy resistance in hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Omega-3 fatty acid DHA induces ferroptosis in colorectal cancer patient-derived organoids and drug-tolerant cells.Cell death & disease · 2026Article
- The phospholipid profile of T cells shapes ACSL4 dependency and ferroptosis sensitivity of naive, effector, and memory T cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Expression of Antioxidant Defense Genes Determines Synergistic Ferroptosis Induction by the Combination of Erastin and Omega-3 Docosahexaenoic Acid in Prostate Cancer Cells.Doklady. Biochemistry and biophysics · 2026Article
- The omega-3 DHA induces pyroptosis and mitochondrial dysfunction in ovarian cancer cells via ROS and caspase-1 activation.Cell death discovery · 2026Article
- Egg-derived sphingomyelin induces ferroptosis in cancer cells, depending on intracellular labile iron pool levels.Biochemistry and biophysics reports · 2025Article
- Effects of plant-derived dietary antioxidants on Alzheimer's disease: Focus on ferroptosis.Asia Pacific journal of clinical nutrition · 2025Review
- Elovl7 sensitizes podocytes to ferroptosis in podocytopathy by elongating polyunsaturated fatty acids.Cell death & disease · 2025Article
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
- Targeting ALOX5 ameliorates renal tubular injury in ischemia-reperfusion-induced acute kidney injury via inhibition of ferroptosis.Communications biology · 2025Article
- Danger zone: The balance between fat-driven health and death.Molecular cell · 2025Article
- The instrumental role of lipids in governing the sensitivity of multiple myeloma to ferroptosis.Discover oncology · 2025Review
- Effects of Docosahexaenoic Acid on Prostate Cancer.Journal of xenobiotics · 2025Review
- Differences in metabolite profiling by cold atmospheric plasma in normal and cancer cells.Journal of bioenergetics and biomembranes · 2025Article
- The Impact of Polyunsaturated Fatty Acids in Cancer and Therapeutic Strategies.Current nutrition reports · 2025Review
- Targeting ferroptosis in prostate cancer management: molecular mechanisms, multidisciplinary strategies and translational perspectives.Journal of translational medicine · 2025Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
purposeFerroptosis is a form of regulated cell death that has the potential to be targeted as a cancer therapeutic strategy. But cancer cells have a wide range of sensitivities to ferroptosis, which limits its therapeutic potential. Accumulation of lipid peroxides determines the occurrence of ferroptosis. However, the type of lipid involved in peroxidation and the mechanism of lipid peroxide accumulation are less studied.
methodsThe effects of fatty acids (10 μM) with different carbon chain length and unsaturation on ferroptosis were evaluated by MTT and LDH release assay in cell lines derived from prostate cancer (PC3, 22RV1, DU145 and LNCaP), colorectal cancer (HT-29), cervical cancer (HeLa) and liver cancer (HepG2). Inhibitors of apoptosis, necroptosis, autophagy and ferroptosis were used to determine the type of cell death. Then the regulation of reactive oxygen species (ROS) and lipid peroxidation by docosahexaenoic acid (DHA) was measured by HPLC-MS and flow cytometry. The avtive form of DHA was determined by siRNA mediated gene silencing. The role of lipoxygenases was checked by inhibitors and gene silencing. Finally, the effect of DHA on ferroptosis-mediated tumor killing was verified in xenografts.
resultsThe sensitivity of ferroptosis was positively correlated with the unsaturation of exogenously added fatty acid. DHA (22:6 n-3) sensitized cancer cells to ferroptosis-inducing reagents (FINs) at the highest level in vitro and in vivo. In this process, DHA increased ROS accumulation, lipid peroxidation and protein oxidation independent of its membrane receptor, GPR120. Inhibition of long chain fatty acid-CoA ligases and lysophosphatidylcholine acyltransferases didn't affect the role of DHA. DHA-involved ferroptosis can be induced in both arachidonate lipoxygenase 5 (ALOX5) negative and positive cells. Down regulation of ALOX5 inhibited ferroptosis, while overexpression of ALOX5 promoted ferroptosis.
conclusionDHA can effectively promote ferroptosis-mediated tumor killing by increasing intracellular lipid peroxidation. Both ALOX5 dependent and independent pathways are involved in DHA-FIN induced ferroptosis. And during this process, free DHA plays an important role.
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