ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Bioactivation of Napabucasin Triggers Reactive Oxygen Species-Mediated Cancer Cell Death.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer.Communications chemistry · 2026Article
- STY12, a Novel NQO1/HDAC Dual-Targeting Agent, Exhibits Potent Anti-Pancreatic Cancer Activity by ROS-Mediated DNA Damage.Biomolecules · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
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- 2-oxoglutarate:acceptor oxidoreductase-catalyzed redox cycling effectively targets coccoid forms of Helicobacter pylori.Nature communications · 2025Article
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- Napabucasin targets resistant triple negative breast cancer through suppressing STAT3 and mitochondrial function.Cancer chemotherapy and pharmacology · 2025Article
- SP600125, a selective JNK inhibitor, is a potent inhibitor of NAD(P)H: quinone oxidoreductase 1 (NQO1).Acta pharmacologica Sinica · 2025Article
- Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.Neuro-oncology · 2025Article
- A small molecule cryptotanshinone induces non-enzymatic NQO1-dependent necrosis in cancer cells through the JNK1/2/Iron/PARP/calcium pathway.Acta pharmaceutica Sinica. B · 2025Article
- STAT3 mediates CAF-induced osimertinib resistance via regulating protein secretion in non-small cell lung cancer.Frontiers in pharmacology · 2025Article
- Napabucasin Inhibits Proliferation and Migration of Glioblastoma Cells (U87) by Regulating JAK2/STAT3 Signaling Pathway.Medicina (Kaunas, Lithuania) · 2024Article
- Targeting the JAK-STAT pathway in colorectal cancer: mechanisms, clinical implications, and therapeutic potential.Frontiers in cell and developmental biology · 2024Review
- Effect of napabucasin and doxorubicin via the Jak2/Stat3 signaling pathway in suppressing the proliferation of neuroblastoma cells.Acta cirurgica brasileira · 2024Article
- The Anticancer Effect of Napabucasin (BBI608), a Natural Naphthoquinone.Molecules (Basel, Switzerland) · 2023Review
- [Procine recombinant NK-lysin inhibits hepatocellular carcinoma metastasis by downregulating FKBP3 and inhibiting oxidative phosphorylation and glycolysis: a proteomic analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Article
- Internally Controlled and Dynamic Optical Measures of Functional Tumor Biology.Analytical chemistry · 2023Article
- Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
purposeNapabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anticancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death. EXPERIMENTAL
designBinding of napabucasin to NAD(P)H:quinone oxidoreductase-1 (NQO1), and other oxidoreductases, was measured. Pancreatic cancer cell lines were treated with napabucasin, and cell survival, ROS generation, DNA damage, transcriptomic changes, and alterations in STAT3 activation were assayed
resultsNapabucasin was found to bind with high affinity to NQO1 and to a lesser degree to cytochrome P450 oxidoreductase (POR). Treatment resulted in marked induction of ROS and DNA damage with an NQO1- and ROS-dependent decrease in STAT3 phosphorylation. Differential cytotoxic effects were observed, where NQO1-expressing cells generating cytotoxic levels of ROS at low napabucasin concentrations were more sensitive. Cells with low or no baseline NQO1 expression also produced ROS in response to napabucasin, albeit to a lesser extent, through the one-electron reductase POR.
conclusionsNapabucasin is bioactivated by NQO1, and to a lesser degree by POR, resulting in futile redox cycling and ROS generation. The increased ROS levels result in DNA damage and multiple intracellular changes, one of which is a reduction in STAT3 phosphorylation.
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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.