ArticleOncogene2023
Repurposed pizotifen malate targeting NRF2 exhibits anti-tumor activity through inducing ferroptosis in esophageal squamous cell carcinoma.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Gambogenic acid globally regulates translational processes in Nrf2-mutant esophageal squamous cell carcinoma by promoting Nrf2/MafG protein multimerization.Acta pharmacologica Sinica · 2026Article
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- Targeting SRSF6 to Enhance Cisplatin Sensitivity by Modulating Redox Balance via NFE2L1 exon 4 Splicing in ESCC.International journal of biological sciences · 2026Article
- Discovery of a novel Nrf2 activator that modulates mitochondrial function in neurons by regulating DHRS3-Nrf2 interaction after ischemic stroke.Theranostics · 2026Article
- The dual roles of ferroptosis in digestive tract tumors: mechanisms, microenvironment regulation, and therapeutic integration with emphasis on immune interactions.Frontiers in immunology · 2026Review
- Rescuing fertility: C-Phycocyanin prevents ovarian damage through NRF2-mediated ferroptosis pathways in polycystic ovary syndrome models.Zoological research · 2025Article
- CERS6 promotes esophageal squamous cell carcinoma proliferation by increasing the stability of RPN1.Cell death discovery · 2025Article
- Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Emerging Ferroptosis Involvement in Amyotrophic Lateral Sclerosis Pathogenesis: Neuroprotective Activity of Polyphenols.Molecules (Basel, Switzerland) · 2025Review
- Significance of Malic Enzyme 1 in Cancer: A Review.Current issues in molecular biology · 2025Review
- Neferine Ameliorates Severe Acute Pancreatitis-Associated Intestinal Injury by Promoting NRF2-mediated Ferroptosis.International journal of biological sciences · 2025Article
- Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma.Acta biochimica et biophysica Sinica · 2024Article
- The Role of Nrf2 in the Regulation of Mitochondrial Function and Ferroptosis in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2024Review
- Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.Cancer cell international · 2024Article
- Overexpression of malic enzyme is involved in breast cancer growth and is correlated with poor prognosis.Journal of cellular and molecular medicine · 2024Article
- Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches.Drug design, development and therapy · 2024Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted therapy attempts are needed to enhance esophageal squamous cell carcinoma (ESCC) patients' overall survival and satisfaction of life. Nuclear factor erythroid 2-related factor 2 (NRF2), as a high-confidence cancer driver gene, controls the antioxidant response, metabolic balance and redox homeostasis in cancer and is regarded as a potent molecular target for cancer treatment. Here, we attempted to find a new NRF2 inhibitor and study the underlying molecular mechanism in ESCC. We found that up-regulated NRF2 protein was negatively correlated with patient prognosis and promoted tumor proliferation in ESCC. Moreover, Pizotifen malate (PZM), a FDA-approved medication, bound to the Neh1 domain of NRF2 and prevented NRF2 protein binding to the ARE motif of target genes, suppressing transcription activity of NRF2. PZM treatment suppressed tumor development in ESCC PDX model by inducing ferroptosis via down-regulating the transcription of GPX4, GCLC, ME1 and G6PD. Our study illustrates that the over expression of NRF2 indicates poor prognosis and promotes tumor proliferation in ESCC. PZM, as a novel NRF2 inhibitor, inhibits the tumor growth by inducing ferroptosis and elucidates a potent NRF2-based therapy strategy for patients with ESCC.
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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.