ArticleJournal of experimental & clinical cancer research : CR2019
Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
190 citing papers in PubMed, 3 syntheses or guidelines pooled it, 308 citations in OpenAlex.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- The Role of Artemisinin and its Derivatives in Cancer Therapy via Ferroptosis: A Systematic Review ofAnti-cancer agents in medicinal chemistry · 2026Pooled it
- Ferroptosis in glioma treatment: Current situation, prospects and drug applications.Frontiers in oncology · 2022Pooled it
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- CRISPR-Based Gene Dependency Screens Reveal Mechanism of BRAF Inhibitor Resistance in Anaplastic Thyroid Cancer.Molecular carcinogenesis · 2026Article
- Targeting Ferroptosis in Glioblastoma: Molecular Mechanisms, Tumor Microenvironment, and Therapeutic Opportunities.Cancers · 2026Review
- Acute hypoxia induces liver mitochondrial and endoplasmic reticulum stress in adult grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- HSPA5 overexpression predicts poor prognosis and drives radioresistance and metastasis in nasopharyngeal carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- The Therapeutic Potential of Dihydroartemisinin in Cancer Treatment.International journal of molecular sciences · 2026Review
- GSH-responsive triple-action photosensitizer nanoplatforms orchestrate cuproptosis-ferroptosis synergy to potentiate antitumor PDT efficacy.Journal of nanobiotechnology · 2026Article
- Ferroptosis-induced immune modulation: a new frontier in glioblastoma therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Ferroptosis in Glioblastoma and Neuroblastoma: Molecular Mechanisms and Novel Therapeutic Strategies.Current issues in molecular biology · 2026Review
- HSPA5 promotes YAP/TAZ stability independently of the Hippo pathway and induces proneural-to-mesenchymal transition in glioblastoma.Cell death & disease · 2026Article
- Dihydroartemisinin Alleviates Neuronal Damage and Seizures in Epileptic Mice by Inhibiting Ferroptosis via the SIRT1/FOXO1/SLC7A11/GPX4 Pathway.CNS neuroscience & therapeutics · 2026Article
- Computational characterization of GRP78 binding sites on mitochondrial GPX4: implications for targeting ferroptosis in triple-negative breast cancer.Scientific reports · 2026Article
130 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundDihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death. However, whether DHA causes ferroptosis in glioma cells and the potential regulatory mechanisms remain unclear.
methodsEffects of DHA on the proliferation, cell death, ROS and lipid ROS generation as well as reduced gluthione consumption were assessed in glioma cells with or without ferroptosis inhibitor. The biological mechanisms by which glioma cells attenuate the pro-ferroptotic effects of DHA were assessed using molecular methods.
resultsDHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation. However, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5). Mechanistically, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4). Subsequent HSPA5 upregulation increased the expression and activity of glutathione peroxidase 4 (GPX4), which neutralized DHA-induced lipid peroxidation and thus protected glioma cells from ferroptosis. Inhibition of the PERK-ATF4-HSPA5-GPX4 pathway using siRNA or small molecules increased DHA sensitivity of glioma cells by increasing ferroptosis both in vitro and in vivo.
conclusionsCollectively, these data suggested that ferroptosis might be a novel anticancer mechanism of DHA in glioma and HSPA5 may serve as a negative regulator of DHA-induced ferroptosis. Therefore, inhibiting the negative feedback pathway would be a promising therapeutic strategy to strengthen the anti-glioma activity of DHA.
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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.