ArticleRedox biology2020
Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to β-lapachone.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Cytotoxic and genotoxic effects of oxime β-lapachone in human cancer cells: selectivity toward NCI-H460 and insights from molecular docking.Human cell · 2026Article
- Shenling Baizhu powder reduced the oxidative stress and mitochondrial damage during ulcerative colitisthe Kelch-like ECH-associated protein 1-NF-E2-related factor 2/nuclear factor kappa B pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Proteomics-Driven Mechanistic Insights into the Anti-Inflammatory Potential of Thinned Apple Polyphenols in a DNBS-Induced Colitis Model in Mice.Journal of proteome research · 2026Article
- Controlled Self-Immolative Release of β-Lapachone via an OptimizedJournal of the American Chemical Society · 2025Article
- NRF2 activation in cancer and overview of NRF2 small molecule inhibitors.Archives of pharmacal research · 2025Review
- Thioredoxin Reductase 1 inhibition triggers ferroptosis in KRAS-independent lung cancers.bioRxiv : the preprint server for biology · 2025Article
- Antioral cancer effects of ginger derivative 3-HDM exert oxidative stress-associated apoptosis and DNA damage.Molecular biology reports · 2025Article
- Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.Biological trace element research · 2025Article
- Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?Cell communication and signaling : CCS · 2024Review
- Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson's Disease According to the Single-Neuron Degeneration Model.Biomolecules · 2024Review
- Review
- Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions.Cell reports. Medicine · 2024Article
- Multifunctional Fe-based coordination polymer nano-bomb modified with β-lapachone and CaOJournal of nanobiotechnology · 2024Article
- Metabolite itaconate in host immunoregulation and defense.Cellular & molecular biology letters · 2023Review
- Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.Marine drugs · 2023Article
- A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression.Nature cancer · 2023Article
- Single-Cell Kinetic Modeling of β-Lapachone Metabolism in Head and Neck Squamous Cell Carcinoma.Antioxidants (Basel, Switzerland) · 2023Article
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alterations in the NRF2/KEAP1 pathway result in the constitutive activation of NRF2, leading to the aberrant induction of antioxidant and detoxification enzymes, including NQO1. The NQO1 bioactivatable agent β-lapachone can target cells with high NQO1 expression but relies in the generation of reactive oxygen species (ROS), which are actively scavenged in cells with NRF2/KEAP1 mutations. However, whether NRF2/KEAP1 mutations influence the response to β-lapachone treatment remains unknown. To address this question, we assessed the cytotoxicity of β-lapachone in a panel of NSCLC cell lines bearing either wild-type or mutant KEAP1. We found that, despite overexpression of NQO1, KEAP1 mutant cells were resistant to β-lapachone due to enhanced detoxification of ROS, which prevented DNA damage and cell death. To evaluate whether specific inhibition of the NRF2-regulated antioxidant enzymes could abrogate resistance to β-lapachone, we systematically inhibited the four major antioxidant cellular systems using genetic and/or pharmacologic approaches. We demonstrated that inhibition of the thioredoxin-dependent system or copper-zinc superoxide dismutase (SOD1) could abrogate NRF2-mediated resistance to β-lapachone, while depletion of catalase or glutathione was ineffective. Interestingly, inhibition of SOD1 selectively sensitized KEAP1 mutant cells to β-lapachone exposure. Our results suggest that NRF2/KEAP1 mutational status might serve as a predictive biomarker for response to NQO1-bioactivatable quinones in patients. Further, our results suggest SOD1 inhibition may have potential utility in combination with other ROS inducers in patients with KEAP1/NRF2 mutations.
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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.