ArticleMolecular cancer research : MCR2012
Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.Blood · 2014Trial
- Metabolic rewiring of the dendritic cell-T cell axis: tumour-derived barriers and therapeutic opportunities.Experimental & molecular medicine · 2026Review
- Development of Prognostic Features and Investigation of Therapeutic Insights Related to Non-Apoptotic Regulatory Cell Death in Colorectal Cancer.Applied biochemistry and biotechnology · 2025Article
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- ROS-activatable Prodrug of Doxazolidine as Novel Cancer Therapy Paradigm.Advanced therapeutics · 2024Article
- Oxidative cell death in cancer: mechanisms and therapeutic opportunities.Cell death & disease · 2024Review
- The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment.Cancers · 2022Review
- Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.Frontiers in aging · 2022Review
- Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin.Molecules (Basel, Switzerland) · 2020Review
- Genome-Scale CRISPR/Cas9 Screening Reveals Squalene Epoxidase as a Susceptibility Factor for Cytotoxicity of Malformin A1.Chembiochem : a European journal of chemical biology · 2019Article
- Understanding of ROS-Inducing Strategy in Anticancer Therapy.Oxidative medicine and cellular longevity · 2019Review
- High EIF2B5 mRNA expression and its prognostic significance in liver cancer: a study based on the TCGA and GEO database.Cancer management and research · 2018Article
- Synthesis and Evaluation of Biological Activities of Aziridine Derivatives of Urea and Thiourea.Molecules (Basel, Switzerland) · 2017Article
- Targeting reactive oxygen species in development and progression of pancreatic cancer.Expert review of anticancer therapy · 2017Review
- New insights into the unfolded protein response in stem cells.Oncotarget · 2016Review
- Altered activity patterns of transcription factors induced by endoplasmic reticulum stress.BMC biochemistry · 2016Article
- Comprehensive Two- and Three-Dimensional RNAi Screening Identifies PI3K Inhibition as a Complement to MEK Inhibitor AS703026 for Combination Treatment of Triple-Negative Breast Cancer.Journal of Cancer · 2015Article
- The orphan nuclear receptor NR4A1 (Nur77) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells.Molecular cancer research : MCR · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative protein folding in the endoplasmic reticulum (ER) requires strict regulation of redox homeostasis. Disruption of the lumenal redox balance induces an integrated ER stress response that is associated with reduced protein translation, increased chaperone activity, and ultimately cell death. Imexon is a small-molecule chemotherapeutic agent that has been shown to bind glutathione (GSH) and induce oxidative stress in tumor cells; however, the mechanism of cytotoxicity is not well understood. In this report, we investigate the effects of imexon on the integrated ER stress response in pancreatic carcinoma cells. Acute exposure to imexon induces an ER stress response characterized by accumulation of the oxidized form of the oxidoreductase Ero1α, phosphorylation of eIF2α, and inhibition of protein synthesis. An RNA interference chemosensitization screen identified the eukaryotic translation initiation factor eIF2B5 as a target that enhanced imexon-induced growth inhibition of MiaPaCa-2 pancreatic cancer cells, but did not significantly augment the effects of imexon on protein synthesis. Concurrent reduction of intracellular thiols with N-acetyl cysteine reversed imexon activity, however cotreatment with superoxide scavengers had no effect, suggesting thiol binding may be a primary component of the oxidative effects of imexon. Moreover, the data suggest that disruption of the redox balance in the ER is a potential therapeutic target.
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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.