ArticleMolecular and cellular biology2022
Mechanism of Erastin-Induced Ferroptosis in MDA-MB-231 Human Breast Cancer Cells: Evidence for a Critical Role of Protein Disulfide Isomerase.
Article in Molecular and cellular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Pterostilbene Attenuates Neuronal Ferroptosis After Traumatic Brain Injury: Involvement of the SIRT1/PGC-1α/NRF2 Signaling Pathway.Molecular neurobiology · 2026Article
- Mechanism of L-Buthionine-(S,R)-sulfoximine-induced ferroptotic cell death in mouse hippocampal neuronal cells.Cell communication and signaling : CCS · 2026Article
- PDIA3 Inhibition Facilitates Sensitivity of IKE-Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting ferroptosis in gefitinib-resistant HCC827 NSCLC cells using erastin.American journal of cancer research · 2026Article
- The promising arsenal of ferroptosis inducers in bladder cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Co-targeting ferroptosis and immune evasion through small molecules in breast cancer.Journal of translational internal medicine · 2025Article
- Characterization of the mechanisms underlying sulfasalazine-induced ferroptotic cell death: role of protein disulfide isomerase-mediated NOS activation and NO accumulation.Acta biochimica et biophysica Sinica · 2025Article
- S-Nitrosylation of p53 in Melanoma Cells Under Nitrosative Stress.International journal of molecular sciences · 2025Article
- Strong protection by bazedoxifene against chemically-induced ferroptotic neuronal death in vitro and in vivo.Cell communication and signaling : CCS · 2025Article
- Protein disulfide isomerase integrates toll-like receptor 4 and P2X7 receptor signaling pathways during lipopolysaccharide-induced neuroinflammation.Scientific reports · 2025Article
- Raloxifene Prevents Chemically-Induced Ferroptotic Neuronal Death In Vitro and In Vivo.Molecular neurobiology · 2025Article
- Ferroptosis Inducers Erastin and RSL3 Enhance Adriamycin and Topotecan Sensitivity in ABCB1/ABCG2-Expressing Tumor Cells.International journal of molecular sciences · 2025Article
- Mechanism of RSL3-induced ferroptotic cell death in HT22 cells: crucial role of protein disulfide isomerase.Acta biochimica et biophysica Sinica · 2024Article
- Protection of HT22 neuronal cells against chemically-induced ferroptosis by catechol estrogens: protein disulfide isomerase as a mechanistic target.Scientific reports · 2024Article
- Protein disulfide isomerase plays a crucial role in mediating chemically-induced, glutathione depletion-associated hepatocyte injury in vitro and in vivo.Cell communication and signaling : CCS · 2024Article
- Mechanisms of Cell Death Induced by Erastin in Human Ovarian Tumor Cells.International journal of molecular sciences · 2024Article
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- The prognostic and antitumor roles of key genes of ferroptosis in liver hepatocellular cancer and stomach adenocarcinoma.Cancer biomarkers : section A of Disease markers · 2024Article
- Redox Biomarkers - An Effective Tool for Diagnosing COVID-19 Patients and Convalescents.Journal of inflammation research · 2024Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a form of regulated cell death resulting predominantly from catastrophic accumulation of lipid reactive oxygen species (ROS). While the antioxidant systems that counter ferroptosis have been well characterized, the mechanism underlying ferroptosis-associated accumulation of lipid ROS remains unclear. In this study, we demonstrated that protein disulfide isomerase (PDI) is a novel mediator of ferroptosis, which is responsible for the accumulation of lipid ROS and ultimately ferroptosis in MDA-MB-231 human breast cancer cells. Treatment with erastin led to a significant increase in inducible nitric oxide synthase (iNOS)-mediated nitric oxide production, which contributes to the accumulation of the death-inducing cellular lipid ROS. Small interfering RNA (siRNA)-mediated PDI knockdown or pharmacological inhibition of PDI's isomerase activity with cystamine strongly suppressed iNOS dimerization and its catalytic activation, subsequently prevented lipid ROS accumulation, and conferred strong protection against erastin-induced ferroptosis. Remarkably, PDI knockdown in MDA-MB-231 cells also largely abrogated the protective effect of cystamine against erastin-induced ferroptotic cell death. Together, these experimental observations demonstrate a noncanonical role of PDI in ferroptosis, which may serve as a potential therapeutic target for ferroptosis-related diseases.
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