ArticleActa pharmacologica Sinica2024
Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- CWH43 Suppresses Ferroptosis-Associated Vulnerability Through Redox Adaptation in Colorectal Cancer.International journal of molecular sciences · 2026Article
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Endogenous glucocorticoids and glucocorticoid receptor signaling: Dual regulators of PD-1/PD-L1 immunotherapy efficacy in the tumor microenvironment.Chinese medical journal · 2026Review
- Geno-guided targeting of ferroptosis: a multi-layered network to overcome radioresistance in lung cancer.Frontiers in cell and developmental biology · 2026Review
- A Degradable Nanoplatform Integrating Glucose Oxidase and Copper Selenide for Near-Infrared-Enhanced Multimodal Synergistic Therapy in Lung Cancer.Biomaterials research · 2026Article
- A guide to reactive oxygen species in tumour hypoxia: measurement and therapeutic implications.Molecular oncology · 2025Review
- Tungsten disulfide atomic crystals with RONS scavenging and liver targeting capabilities for acetaminophen-induced acute liver injury therapy.Journal of nanobiotechnology · 2025Article
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Article
- Oxidative Stress Defense Module in Lung Cancers: Molecular Pathways and Therapeutic Approaches.Antioxidants (Basel, Switzerland) · 2025Review
- Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
- Review
- MISP Suppresses Ferroptosis via MST1/2 Kinases to Facilitate YAP Activation in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy.Frontiers in oncology · 2025Review
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- Advances in mitochondrial dysfunction in radiation tissue injury.Frontiers in physiology · 2025Review
- New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease.Cell death & disease · 2024Review
- The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.Acta pharmacologica Sinica · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combining radiotherapy with Nrf-2 inhibitor holds promise as a potential therapeutic strategy for radioresistant lung cancer. Here, the radiosensitizing efficacy of a synthetic glucocorticoid clobetasol propionate (CP) in A549 human lung cancer cells was evaluated. CP exhibited potent radiosensitization in lung cancer cells via inhibition of Nrf-2 pathway, leading to elevation of oxidative stress. Transcriptomic studies revealed significant modulation of pathways related to ferroptosis, fatty acid and glutathione metabolism. Consistent with these findings, CP treatment followed by radiation exposure showed characteristic features of ferroptosis in terms of mitochondrial swelling, rupture and loss of cristae. Ferroptosis is a form of regulated cell death triggered by iron-dependent ROS accumulation and lipid peroxidation. In combination with radiation, CP showed enhanced iron release, mitochondrial ROS, and lipid peroxidation, indicating ferroptosis induction. Further, iron chelation, inhibition of lipid peroxidation or scavenging mitochondrial ROS prevented CP-mediated radiosensitization. Nrf-2 negatively regulates ferroptosis through upregulation of antioxidant defense and iron homeostasis. Interestingly, Nrf-2 overexpressing A549 cells were refractory to CP-mediated ferroptosis induction and radiosensitization. Thus, this study identified anti-psoriatic drug clobetasol propionate can be repurposed as a promising radiosensitizer for Keap-1 mutant lung cancers.
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