ArticleInternational journal of biological sciences2023
Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation.
Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Emerging research themes in ferroptosis research for non-small cell lung cancer: a bibliometric and visualized analysis.Frontiers in immunology · 2025Pooled it
- FGF8-mediated TRIM16 regulation promotes K48-linked ubiquitination and degradation of RIG-I to facilitate Influenza a virus immune evasion.Virulence · 2026Article
- Hypoxia-ROS-HSP Triad Axis in Cancer: Mechanisms, Crosstalk, and Therapeutic Implications.Cells · 2026Review
- Timosaponin AIII-based liposomes loaded with Auranofin for the induction of ferroptosis in anaplastic thyroid carcinoma.Journal of cancer research and clinical oncology · 2026Article
- Heat Shock Proteins as Cancer Biomarkers: From Mechanism to Clinical Application.Molecular diagnosis & therapy · 2026Review
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Steroidogenesis is associated with bladder cancer progression via reprogramming the metabolic landscape of the tumor immune microenvironment.Discover oncology · 2026Article
- Research Progress on Chinese Herbal Medicine Components Targeting Ferroptosis for Cancer Therapy.Molecules (Basel, Switzerland) · 2026Review
- Research status and challenges of anti-tumor effects of natural saponins and their combination therapy.Journal of the Egyptian National Cancer Institute · 2026Review
- Lactylation of β-catenin promotes non-small cell lung cancer by inhibiting ferroptosis through TCF4-mediated GPX4 transcription.Journal of translational medicine · 2026Article
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- PTK6 suppresses NSCLC ferroptosis by promoting m6A-YTHDF2-dependent FOXO3 mRNA degradation through phosphorylation.Molecular genetics and genomics : MGG · 2026Article
- CircAFF4 inhibits lung cancer progression via destabilizing GPX4 and triggering ferroptosis.Biology direct · 2026Article
- NCOA4-Mediated Ferritinophagy Induces Ferroptosis and Enriches Ferritin-Containing EVs via Ferritin Phase Separation to Promote Mechanical Ventilation-Induced Pulmonary Fibrosis.Journal of advanced research · 2026Article
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Anti-cancer mechanism of traditional Chinese medicine natural products targeting ferroptosis.Chinese medicine · 2026Review
- Erianin Disturbs Iron and ROS Homeostasis To Trigger Ferroptosis in Colorectal Cancer Cells.Cell biochemistry and biophysics · 2026Article
- CB2R-mediated GPX4 stabilization: a new avenue for treating cognitive impairment in elderly migraine patients.The journal of headache and pain · 2026Article
- FBR-NDs: a ferroptosis-inducing nanocomplex for targeted breast cancer therapy via immune modulation and redox-responsive drug delivery.Breast cancer research : BCR · 2026Article
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and
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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.