ArticleACS omega2024
ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells.
Article in ACS omega, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
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Who cites it
18 citing papers in PubMed.
- Celastrol alleviates synovial inflammation and joint destruction in rheumatoid arthritis in association with Nrf2/HO-1/GPX4 pathway activation.Molecular and cellular biochemistry · 2026Article
- Hydrogen Sulfide Suppresses RANKL-Induced Osteoclast Differentiation by Modulating Nrf2/GPX4 Signaling.Physiological research · 2026Article
- Integrated bioinformatics analyses and cell line experiments implicate miR-33a-5p/HIF1A in the cellular response to celastrol in lung adenocarcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Asperosaponin VI Ameliorates Spontaneous Abortion by Inhibiting Trophoblast Ferroptosis via the KEAP1/NRF2/GPX4 Axis.Antioxidants (Basel, Switzerland) · 2026Article
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- The Antitumor Potential of Celastrol: Research Progress on Antitumor Mechanisms and Strategies for Toxicity Reduction with Efficacy Enhancement.Biomolecules · 2026Review
- Astragaloside IV AlleviatesAntioxidants (Basel, Switzerland) · 2026Article
- A novel anti-acute lung injury mechanism of astilbin: inhibition of epithelial cells ferroptosis by targeting NRF2 activation via binding Val608 site of NRF2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Combination of B-AP15 and HSP90 inhibitor tanespimycin induces ROS-mediated cytotoxicity in human lung cancer cells.BMC pharmacology & toxicology · 2025Article
- The Redox Paradox: Cancer's Double-Edged Sword for Malignancy and Therapy.Antioxidants (Basel, Switzerland) · 2025Review
- A comprehensive review on the role of plant-derived bioactive metabolites driving ROS-mediated apoptosis in cancer.Medical oncology (Northwood, London, England) · 2025Review
- Panobinostat potentiates adagrasib-induced cell death by triggering autophagy in human non-small cell lung cancer.Cell death discovery · 2025Article
- Targeting TNFAIP2 with NIR-II CRISPR-Cas9 nanosystem to overcome cisplatin resistance in laryngeal cancer.NPJ precision oncology · 2025Article
- The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis.Molecules (Basel, Switzerland) · 2025Article
- Exosomes derived from umbilical cord blood NK cells inhibit the progression of pancreatic cancer by targeting ROS-mediated mitochondrial dysfunction.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- An Inhaled Nanoemulsion Encapsulating a Herbal Drug for Non-Small Cell Lung Cancer (NSCLC) Treatment.Pharmaceutics · 2025Article
- Article
- Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway.Open life sciences · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is one of the leading causes of death. Celastrol is a natural product that has shown anticancer activity but has not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered that celastrol stimulates an abnormal rise in the reactive oxygen species (ROS) level in lung cancer cells and that the ROS scavenger N-acetylcysteine (NAC) could counteract the cell death caused by celastrol. At the same time, celastrol upregulated the expression of cytoprotective transcription factor Nrf2 and its downstream proteins, which are effective in preventing the oxidative damage caused by ROS accumulation. Notably, we found that the overexpression of Nrf2 enhances the tolerance of lung cancer cells to celastrol and that lung cancer cells H460 with a Keap1 mutation are insensitive to celastrol. This indicates that the increase in Nrf2 contributes to the survival of lung cancer cells. Thus, we brought in an Nrf2 inhibitor ML385 to suppress the activation of Nrf2. We found that when ML385 and celastrol were added together the survival rates of lung cancer cells decreased more and the detected ROS level became much higher compared to treatment with celastrol alone. We also discovered that ML385 suppressed the expression of HO-1 and GCLC, which amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study found that ML385 enhanced celastrol-induced increases in ROS and ER stress, leading to lung cancer cell death. This research provides a potential strategy for the preclinical investigation of celastrol.
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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.