ArticleFree radical biology & medicine2017
Low-density lipoprotein docosahexaenoic acid nanoparticles induce ferroptotic cell death in hepatocellular carcinoma.
Article in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 3 of them syntheses that pooled it.
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Who cites it
102 citing papers in PubMed, 3 syntheses or guidelines pooled it, 172 citations in OpenAlex.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- Metabolic cell death in cancer: mechanisms and therapeutic potential.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Mapping the evolution and research landscape of ferroptosis-targeted nanomedicine: insights from a scientometric analysis.Frontiers in pharmacology · 2024Pooled it
- Targeting ferroptosis induction via nanomaterials in hepatocellular carcinoma: an insight into mechanism and therapeutic potential.Journal of nanobiotechnology · 2026Review
- Ferroptosis-induced immune modulation: a new frontier in glioblastoma therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Recent Advancements in Drug Targeting for Ferroptosis as an Antitumor Therapy: Development of Novel therapeutics.Current cancer drug targets · 2026Review
- Effects of plant-derived dietary antioxidants on Alzheimer's disease: Focus on ferroptosis.Asia Pacific journal of clinical nutrition · 2025Review
- Article
- Exploring Long Noncoding RNAs as Regulators of Tumor Ferroptosis: Advances and Challenges.Cancer science · 2025Review
- Therapeutic potential of synthetic and natural iron chelators against ferroptosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.Frontiers in immunology · 2025Review
- DHA and Cancer: The Uncharted Territory of Nutritional Oncology.Current pharmaceutical biotechnology · 2025Article
- Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.Nutrients · 2024Article
- APT imaging of hepatocellular carcinoma signals an effective therapeutic response in advance of tumor shrinkage.Hepatic oncology · 2024Article
- [High expression of SLC2A1 inhibits ferroptosis and promotes proliferation and invasion of lung adenocarcinoma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Therapeutic types and advantages of functionalized nanoparticles in inducing ferroptosis in cancer therapy.Annals of medicine · 2024Review
- Ferroptosis: a new promising target for hepatocellular carcinoma therapy.Molecular and cellular biochemistry · 2024Review
- Nanomedicine-induced programmed cell death enhances tumor immunotherapy.Journal of advanced research · 2024Review
- Recent progress of ferroptosis in cancers and drug discovery.Asian journal of pharmaceutical sciences · 2024Review
- Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines. Following LDL-DHA treatment both rat and human HCC cells experience pronounced lipid peroxidation, depletion of glutathione and inactivation of the lipid antioxidant glutathione peroxidase-4 (GPX4) prior to cell death. Inhibitor studies revealed that the treated HCC cells die independent of apoptotic, necroptotic or autophagic pathways, but require the presence of cellular iron. These hallmark features are consistent and were later confirmed to reflect ferroptosis, a novel form of nonapoptotic iron-dependent cell death. In keeping with the mechanisms of ferroptosis cell death, GPX4 was also found to be a central regulator of LDL-DHA induced tumor cell killing. We also investigated the effects of LDL-DHA treatments in mice bearing human HCC tumor xenografts. Intratumoral injections of LDL-DHA severely inhibited the growth of HCC xenografts long term. Consistent with our in vitro findings, the LDL-DHA treated HCC tumors experienced ferroptotic cell death characterized by increased levels of tissue lipid hydroperoxides and suppression of GPX4 expression.
conclusionLDL-DHA induces cell death in HCC cells through the ferroptosis pathway, this represents a novel molecular mechanism of anticancer activity for LDL-DHA nanoparticles.
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Registered trials
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.