ArticleNature communications2018
Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Topical niclosamide (ATx201) reduces Staphylococcus aureus colonization and increases Shannon diversity of the skin microbiome in atopic dermatitis patients in a randomized, double-blind, placebo-controlled Phase 2 trial.Clinical and translational medicine · 2022Trial
- Slick K+ channels contribute to cardiac remodeling, fibrosis, and dysfunction in postinfarction hearts.JCI insight · 2026Article
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- A Novel Niclosamide Sulfate Prodrug with Enhanced Bioavailability Suppresses Hepatocellular Carcinoma via Inhibition of Multiple Signaling Pathways.bioRxiv : the preprint server for biology · 2026Article
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- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology.Cancers · 2024Review
- The 2-oxoglutarate/malate carrier extends the family of mitochondrial carriers capable of fatty acid and 2,4-dinitrophenol-activated proton transport.Acta physiologica (Oxford, England) · 2024Article
- Niclosamide - encapsulated lipid nanoparticles for the reversal of pulmonary fibrosis.Materials today. Bio · 2024Article
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Review
- Construction and validation of a novel ferroptosis-related prognostic signature for lung adenocarcinoma.Translational lung cancer research · 2023Article
- Loss of TP53 cooperates with c-MET overexpression to drive hepatocarcinogenesis.Cell death & disease · 2023Article
- Combination of Niclosamide and Pirfenidone Alleviates Pulmonary Fibrosis by Inhibiting Oxidative Stress and MAPK/Nf-κB and STATs Regulated Genes.Pharmaceuticals (Basel, Switzerland) · 2023Article
- TP53 Alterations in Myelodysplastic Syndromes and Acute Myeloid Leukemia.Biomedicines · 2023Review
- Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma.Cancer research · 2023Article
- Salicylanilides and Their Anticancer Properties.International journal of molecular sciences · 2023Review
- In Vitro Evaluation and Mitigation of Niclosamide's Liabilities as a COVID-19 Treatment.Vaccines · 2022Article
- SAR study of niclosamide derivatives in the human glioblastoma U-87 MG cells.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- In Vitro Evaluation and Mitigation of Niclosamide's Liabilities as a COVID-19 Treatment.bioRxiv : the preprint server for biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
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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.