ArticleCell death & disease2022
HIF-α activation by the prolyl hydroxylase inhibitor roxadustat suppresses chemoresistant glioblastoma growth by inducing ferroptosis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Ferroptosis-Based Nanotherapeutic Strategies to Overcome Temozolomide Resistance in Glioblastoma: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2026Pooled it
- Clinically approved HIF-PHIs modulate redox metabolism, cell growth, and angiogenesis independent of HIF-1α/HIF-2α.Redox biology · 2026Article
- Acriflavine-empowered IR780-PTX albumin nanoparticles for reinforced synergistic photochemotherapy.Advanced biotechnology · 2026Article
- Astrocytic PCBP1 Suppresses Ferroptosis to Restore Glutamatergic Homeostasis and Mitigate Stress-Induced Depression in Male Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adaptaquin is selectively toxic to glioma stem cells through disruption of iron and cholesterol metabolism.Molecular oncology · 2026Article
- Mechanistic Evaluation of Roxadustat for Pulmonary Fibrosis: Integrating Network Pharmacology, Transcriptomics, and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Comprehensive exploration of the role of multimodal programmed cell death- associated lncRNAs in the prognosis and immunity of glioma.Frontiers in immunology · 2026Article
- Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects.Experimental & molecular medicine · 2025Review
- Article
- Metformin alleviates renal tubular injury in diabetic kidney disease by activating mitophagy and inhibiting ferroptosis via HIF-1α/MIOX axis.Journal of pharmaceutical analysis · 2025Article
- Ferroptosis as a therapeutic target in glioblastoma: Mechanisms and emerging strategies.Molecular therapy. Nucleic acids · 2025Review
- Ioning out glioblastoma: ferroptosis mechanisms and therapeutic frontiers.Cell death discovery · 2025Review
- Deciphering the role of circular RNAs in cancer progression under hypoxic conditions.Medical oncology (Northwood, London, England) · 2025Review
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis.Bone research · 2025Article
- Mitochondrial Reactive Oxygen Species (mROS) Generation and Cancer:International journal of nanomedicine · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with glioblastoma (GBM) have poor prognosis and limited treatment options, largely due to therapy resistance upon the induction of apoptosis. Ferroptosis emerges as a potential antineoplastic strategy to bypass apoptosis resistance in traditional therapeutics. Hypoxia is a fundamental hallmark of GBM and hypoxia-inducible factor (HIF) is the main regulator of hypoxia response, however, the role of HIF has not been sufficiently explored in GBM. Herein, we first discovered that amplifying HIF signals by the prolyl hydroxylase (PHD) inhibitor roxadustat significantly suppressed GBM cell growth in vitro and in vivo, especially when the cells were resistant to temozolomide (TMZ). The accumulation of lipid peroxidation and cellular iron in GBM cells following roxadustat treatment indicated that the cells underwent ferroptosis, which was also supported by morphological changes in mitochondrial ultrastructure and immunogenic signals release. Moreover, in vivo studies further confirmed the ferroptosis induction and verified that roxadustat significantly prolonged survival of the mice harboring chemoresistant GBM without visible organ toxicity. Finally, we proved that the ferroptosis induction by roxadustat is HIF-α independent, especially activation of HIF-2α upregulating lipid regulatory genes was revealed to be mainly responsible for the enhanced lipid peroxidation. Altogether, our study provided novel evidence that amplifying HIF signals induced ferroptosis in chemoresistant GBM cells and suppressed the tumor growth in vivo, highlighting that ferroptosis induction by targeting HIF-α might provide new approaches to improve GBM treatment.
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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.