ArticleAntioxidants (Basel, Switzerland)2021
Necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 56 citations in OpenAlex.
- Stereochemical Aspects in the Context of the Structure-Activity Relationship of Chlorido[Journal of medicinal chemistry · 2026Article
- In Vitro Evaluation of Necrostatin-1 Microparticles for Limiting Stress-induced Cell Death and Preserving Islet Function.Transplantation direct · 2026Article
- RIP kinase inhibition with Necrostatin-1 improves human marginal mass islet graft survival and function for the management of type 1 diabetes.Cell death & disease · 2026Article
- Predicting DNA damage response using synthetic cell painting profiles and experimental analysis.iScience · 2026Article
- Ferroptosis and Its Crosstalk with Other Cell Death Modes in Ischemic Stroke.Current medicinal chemistry · 2026Review
- PANoptosis in diabetic retinopathy: immunological insights into mechanisms and translational therapies.Frontiers in immunology · 2026Review
- Exploring the Potential Role of Manganese-Based Zeolitic Imidazolate Framework Nanoparticles in Cancer Therapy:International journal of nanomedicine · 2026Article
- Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen.International journal of molecular sciences · 2025Article
- Ginsenoside (20)S-APPT induces ferroptosis in hepatocellular carcinoma and cholangiocarcinoma by targeting FSP1.Acta pharmacologica Sinica · 2025Article
- Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy.Cell death discovery · 2025Article
- Neuronal Damage Induced by Gradual Oxidative Stress in iPSC-Derived Neurons: Implications for Ferroptosis Involvement and ALS Drug Evaluation.Journal of neurochemistry · 2025Article
- Dovitinib Ameliorates Inflammation-Related Diseases by Inhibiting Necroptosis and Ferroptosis.ACS chemical biology · 2025Article
- Article
- Potent ferroptosis agent RSL3 induces cleavage of Pyroptosis-Specific gasdermins in Cancer cells.Scientific reports · 2025Article
- Ferroptosis-activating metabolite acrolein antagonizes necroptosis and anti-cancer therapeutics.Nature communications · 2025Article
- RIPK1: A Promising Target for Intervention Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Programmed cardiomyocyte death in myocardial infarction.Apoptosis : an international journal on programmed cell death · 2025Review
- Insights on the crosstalk among different cell death mechanisms.Cell death discovery · 2025Review
- Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.Recent patents on anti-cancer drug discovery · 2025Article
- Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria.Cell death & disease · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ferroptosis is caused by the iron-mediated accumulation of lipid peroxidation, which is distinct from apoptosis and necroptosis. Necrostatin-1 inhibits receptor-interacting serine/threonine-protein kinase 1 (RIPK1) to initiate necroptosis; it also inhibits indoleamine 2,3-dioxygenase (IDO) to regulate tumor immunity. However, few studies have examined the off-target effect of necrostatin-1 on the ferroptosis pathway. The present study examined whether necrostatin-1 could interrupt ferroptosis induced by system xc- inhibitors (sulfasalazine and erastin) and a glutathione peroxidase 4 inhibitor (RSL3) in Huh7 and SK-HEP-1 cells. Necrostatin-1 completely prevented decreases in cell viability induced by sulfasalazine and erastin; it partially blunted decreases in cell viability induced by RSL3. Necrostatin-1, ferrostatin-1, and deferoxamine repressed sulfasalazine-provoked membrane permeabilization, as detected by 7-aminoactinomycin D staining and lipid peroxidation measured using a C11-BODIPY probe. However, other RIPK1 inhibitors (necrostatin-1s and GSK2982772) and an IDO inhibitor (1-methyl-D-tryptophan) did not recover the decrease in cell viability induced by sulfasalazine. Necrostatin-1 potentiated sulfasalazine-induced expression of xCT, a catalytic subunit of system xc- in these cells. These results demonstrated that necrostatin-1 blocked ferroptosis through a mechanism independent from RIPK1 and IDO inhibition in Huh7 and SK-HEP-1 cells, indicating that its antioxidant activity should be considered when using necrostatin-1 as a RIPK1 inhibitor.
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