ArticleJournal of hematology & oncology2021
Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells.
Article in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 248 papers, 1 of them a synthesis that pooled it.
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Who cites it
248 citing papers in PubMed, 1 synthesis or guideline pooled it, 415 citations in OpenAlex.
- Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).International journal of oncology · 2024Pooled it
- Anesthesia inhalation agent sevoflurane induces perioperative cognitive impairment: Apelin/early growth response 1 axis induces ferritinophagy and exacerbates ferroptosis.Medical gas research · 2027Article
- Ubiquitylome analysis reveals the protective effect of α-lipoic acid via the ferroptosis pathway during recovery after hepatic oxidative stress in finishing pigs.Stress biology · 2026Article
- Cardiovascular Toxicity in Cancer Therapy: Potential Mechanisms of Ferroptosis and Treatment Strategies.Cells · 2026Review
- Review
- Ferroptosis induction by curcumin through regulating the expression of glutathione peroxidase 4 in papillary thyroid carcinoma.Journal of molecular histology · 2026Article
- Cepharanthine suppresses lung adenocarcinoma through targeting glutathione peroxidase 4.Oncology letters · 2026Article
- The role of ferroptosis in the pathogenesis and treatment of breast cancer.Journal of translational medicine · 2026Review
- Tumor cell ferroptosis in antitumor immunity and immunotherapy efficacy.Journal for immunotherapy of cancer · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism.Respiratory research · 2026Article
- Aberrant expression of TRIM26 suppresses ferroptosis through regulating GPX4 protein stability in colorectal cancer.Molecular biology reports · 2026Article
- Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies.Experimental hematology & oncology · 2026Review
- Looking at the fraction with Annexin V⁺ and propidium iodide⁺: insights into cell death types from preclinical studies in solid and haematological cancers.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Lipid Metabolism and Ferroptosis Resistance in Dormant Breast Cancer Cells: Emerging Therapeutic Vulnerabilities.Diagnostics (Basel, Switzerland) · 2026Review
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Biomimetic hybrid membrane-coated nanoparticles loaded with rhein-iron complex enhance ferroptosis and immunotherapy for triple-negative breast cancer.Materials today. Bio · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
188 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of breast cancer. There is an urgent need for identification of therapeutic agents with unique mode of action for overcoming current challenges in TNBC treatment.
methodsDifferent inhibitors were used to study the cell death manner of DMOCPTL. RNA silencing was used to evaluate the functions of GPX4 in ferroptosis and apoptosis of TNBC cells and functions of EGR1 in apoptosis. Immunohistochemical assay of tissue microarray were used for investigating correlation of GPX4 and EGR1 with TNBC. Computer-aided docking and small molecule probe were used for study the binding of DMOCPTL with GPX4.
resultsDMOCPTL, a derivative of natural product parthenolide, exhibited about 15-fold improvement comparing to that of the parent compound PTL for TNBC cells. The cell death manner assay showed that the anti-TNBC effect of DMOCPTL mainly by inducing ferroptosis and apoptosis through ubiquitination of GPX4. The probe of DMOCPTL assay indicated that DMOCPTL induced GPX4 ubiquitination by directly binding to GPX4 protein. To the best of our knowledge, this is the first report of inducing ferroptosis through ubiquitination of GPX4. Moreover, the mechanism of GPX4 regulation of apoptosis is still obscure. Here, we firstly reveal that GPX4 regulated mitochondria-mediated apoptosis through regulation of EGR1 in TNBC cells. Compound 13, the prodrug of DMOCPTL, effectively inhibited the growth of breast tumor and prolonged the lifespan of mice in vivo, and no obvious toxicity was observed.
conclusionsThese findings firstly revealed novel manner to induce ferroptosis through ubiquitination of GPX4 and provided mechanism for GPX4 inducing mitochondria-mediated apoptosis through up-regulation of EGR1 in TNBC cells. Moreover, compound 13 deserves further studies as a lead compound with novel mode of action for ultimate discovery of effective anti-TNBC drug.
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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.