ArticleHepatology (Baltimore, Md.)2019
Induction of Oxidative Stress Through Inhibition of Thioredoxin Reductase 1 Is an Effective Therapeutic Approach for Hepatocellular Carcinoma.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 174 citations in OpenAlex.
- Thioredoxin reductase-1 facilitates cellular plasticity and stemness mediated by TGF-β1 in non-small cell lung cancer.Cancer biology & therapy · 2026Article
- Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases.Pharmaceutics · 2026Review
- Development of a four-gene prognostic signature for hepatocellular carcinoma using TCGA and GEO datasets.Discover oncology · 2026Article
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Bioinformatics analysis and experimental approach identify BRD-family geneTranslational andrology and urology · 2026Article
- Ebselen: A Multifaceted Organoselenium Compound With Therapeutic Potential in Liver Diseases.Oxidative medicine and cellular longevity · 2026Review
- Auranofin, identified by FDA-approved drug library screening, inhibits HBs antigen secretion via lysosomal damage.PloS one · 2026Article
- ChaC1-based drug screenings identify a synergistic lethal effect of auranofin and proteasome inhibitors in hepatocellular carcinoma cells.Cell death discovery · 2025Article
- Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Investigation of the effects of monosodium glutamate and tannic acid on the glutathione and thioredoxin systems in the liver of rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- ToxAssay: a hierarchical model-driven tool for advanced toxicogenomics biomarker discovery.Bioinformatics (Oxford, England) · 2025Article
- Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation.Nature communications · 2025Article
- Gene Expression Profiling of Advanced Stage Hepatocellular Carcinoma: A Bioinformatic Analysis.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Sevelamer Ameliorates Early Cirrhosis and Inhibits Its Progression towards Hepatocellular Carcinoma in a Diethylnitrosamine-induced Rat Model.Journal of cancer prevention · 2025Article
- Celastrol alleviates esophageal stricture in rats by inhibiting NLR family pyrin domain containing 3 activation.World journal of gastroenterology · 2025Article
- Reactive Oxygen Species: From Tumorigenesis to Therapeutic Strategies in Cancer.Cancer medicine · 2025Review
- A new opportunity for N-acetylcysteine. An outline of its classic antioxidant effects and its pharmacological potential as an epigenetic modulator in liver diseases treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression.Nature communications · 2025Article
- Pifithrin-μ sensitizes mTOR-activated liver cancer to sorafenib treatment.Cell death & disease · 2025Article
- The Effects of Anthropogenic Stressors on Above- and Belowground Phytochemical Diversity of the Wetland Grass,Plants (Basel, Switzerland) · 2024Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide which lacks effective treatment. Cancer cells experience high levels of oxidative stress due to increased generation of reactive oxygen species (ROS). Increased antioxidant-producing capacity is therefore found in cancer cells to counteract oxidative stress. The thioredoxin system is a ubiquitous mammalian antioxidant system which scavenges ROS, and we demonstrate that it is vital for HCC growth as it maintains intracellular reduction-oxidation (redox) homeostasis. Transcriptome sequencing in human HCC samples revealed significant overexpression of thioredoxin reductase 1 (TXNRD1), the cytosolic subunit and key enzyme of the thioredoxin system, with significant correlations to poorer clinicopathological features and patient survival. Driven by the transcriptional activation of nuclear factor (erythroid-derived 2)-like 2, the master protector against oxidative stress, TXNRD1 counteracts intracellular ROS produced in human HCC. Inhibition of TXNRD1 through genetic inhibition hindered the proliferation of HCC cells and induced apoptosis in vitro. Administration of the pharmacological TXNRD1 inhibitor auranofin (AUR) effectively suppressed the growth of HCC tumors induced using the hydrodynamic tail vein injection and orthotopic implantation models in vivo. Furthermore, AUR sensitized HCC cells toward the conventional therapeutic sorafenib. Conclusion: Our study highlights the reliance of HCC cells on antioxidants for redox homeostasis and growth advantage; targeting TXNRD1 resulted in dramatic accumulation of ROS, which was found to be an effective approach for the suppression of HCC tumor growth.
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