ArticleCell death discovery2021
NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent manner.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- TERT drives liver tumorigenesis beyond telomere elongation.Life science alliance · 2026Article
- METTL3 promotes proliferation and invasion and inhibits ferroptosis in hepatocellular carcinoma by mediating m6A methylation modification of NUPR1.Molecular and cellular biochemistry · 2026Article
- A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions.Nature communications · 2026Article
- Nuclear protein 1 is a cell death regulator in primary human airway epithelial cells and reduced in idiopathic pulmonary fibrosis.Scientific reports · 2026Article
- NUPR1 as a central stress-adaptation node in cancer: integrating metabolic rewiring, cell death, and therapy resistance.Journal of biomedical science · 2026Review
- Targeting PTDSS1 to modulate GSH synthesis triggers mitophagy and induces ferroptosis in esophageal squamous cell carcinoma cells.Cell death & disease · 2026Article
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Mitochondria-driven ferroptosis in intervertebral disc degeneration: A novel target in age-related spinal diseases (Review).Experimental and therapeutic medicine · 2026Review
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- NUPR1 in breast cancer: mechanisms and potential applications.Frontiers in physiology · 2026Review
- Histone H4K8 lactylation promotes glioblastoma progression by inducing NUPR1-mediated autophagosome‒lysosome fusion.Theranostics · 2026Article
- Targeting intrinsically disordered nuclear protein 1 (NUPR1) with single-domain antibodies alleviates triple-negative breast cancer (TNBC) progression in vivo.Cell death & disease · 2025Article
- Adaptation of redox metabolism in drug-tolerant persister cells is a vulnerability to prevent relapse in pancreatic cancer.Oncogenesis · 2025Article
- Synergistic antitumor activity of sorafenib and the NUPR1 inhibitor LZX-2-73 in multiple cancer models.Cell death & disease · 2025Article
- SUMO2 inhibits ACSL3 protein degradation to antagonize erastin-induced ferroptosis in hepatocellular carcinoma.Discover oncology · 2025Article
- Donafenib Induces Mitochondrial Dysfunction in Liver Cancer Cells via DRP1.Cell biochemistry and biophysics · 2025Article
- Lactylation-Driven NUPR1 Promotes Immunosuppression of Tumor-Infiltrating Macrophages in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is an iron-dependent cell death characterized by the accumulation of hydroperoxided phospholipids. Here, we report that the NUPR1 inhibitor ZZW-115 induces ROS accumulation followed by a ferroptotic cell death, which could be prevented by ferrostatin-1 (Fer-1) and ROS-scavenging agents. The ferroptotic activity can be improved by inhibiting antioxidant factors in pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells. In addition, ZZW-115-treatment increases the accumulation of hydroperoxided lipids in these cells. We also found that a loss of activity and strong deregulation of key enzymes involved in the GSH- and GPX-dependent antioxidant systems upon ZZW-115 treatment. These results have been validated in xenografts induced with PDAC- and HCC-derived cells in nude mice during the treatment with ZZW-115. More importantly, we demonstrate that ZZW-115-induced mitochondrial morphological changes, compatible with the ferroptotic process, as well as mitochondrial network disorganization and strong mitochondrial metabolic dysfunction, which are rescued by both Fer-1 and N-acetylcysteine (NAC). Of note, the expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. Altogether, these results demonstrate that the mitochondrial cell death mediated by NUPR1 inhibitor ZZW-115 is fully rescued by Fer-1 but also via TFAM complementation. In conclusion, TFAM could be considered as an antagonist of the ferroptotic cell death.
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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.