ArticleBiomolecules & therapeutics2020
Auranofin Enhances Sulforaphane-Mediated Apoptosis in Hepatocellular Carcinoma Hep3B Cells through Inactivation of the PI3K/Akt Signaling Pathway.
Article in Biomolecules & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Sulforaphane Synergies with Phytochemicals and Pharmaceuticals: Implications for Healthspan.Medicines (Basel, Switzerland) · 2026Review
- Inhibiting autophagy enhances anti-cancer properties of sulforaphane.Scientific reports · 2026Article
- Sulforaphane: a natural organosulfur having potential to modulate apoptosis and survival signalling in cancer.Discover oncology · 2025Review
- Glabridin-Gold(I) Complex as a Novel Immunomodulatory Agent Targeting TrxR and MAPK Pathways for Synergistic Enhancement of Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Assessing Auranofin for Second-Line Use in Chemoresistant Ovarian Cancer: Effects on Tumour Spheroid and Primary Cell Growth.Journal of cellular and molecular medicine · 2025Article
- Functional utility of gold complexes with phosphorus donor ligands in biological systems.Coordination chemistry reviews · 2025Article
- Sulforaphane Effects on Neuronal-like Cells and Peripheral Blood Mononuclear Cells Exposed to 2.45 GHz Electromagnetic Radiation.International journal of molecular sciences · 2024Article
- Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway.Journal of Cancer · 2024Article
- Design, Synthesis and Antitumor Activity of Novel Selenium-Containing Tepotinib Derivatives as Dual Inhibitors of c-Met and TrxR.Molecules (Basel, Switzerland) · 2023Article
- Induction of apoptotic cell death in human bladder cancer cells by ethanol extract ofNutrition research and practice · 2022Article
- Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistance and to increase drug effectiveness.Medicinal research reviews · 2022Review
- mTOR inhibitor PP242 increases antitumor activity of sulforaphane by blocking Akt/mTOR pathway in esophageal squamous cell carcinoma.Molecular biology reports · 2022Article
- Schisandrae Fructus ethanol extract attenuates particulate matter 2.5-induced inflammatory and oxidative responses by blocking the activation of the ROS-dependent NF-κB signaling pathway.Nutrition research and practice · 2021Article
- Suppression of Lipopolysaccharide-Induced Inflammatory and Oxidative Response by 5-Aminolevulinic Acid in RAW 264.7 Macrophages and Zebrafish Larvae.Biomolecules & therapeutics · 2021Article
- Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway.Pharmaceutics · 2021Article
- Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma.International journal of molecular sciences · 2021Review
- Gold(I) Phosphine Derivatives with Improved Selectivity as Topically Active Drug Leads to Overcome 5-Nitroheterocyclic Drug Resistance inJournal of medicinal chemistry · 2021Article
- ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts.International journal of molecular sciences · 2021Article
- Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential.Molecules (Basel, Switzerland) · 2021Article
- Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking CaInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.
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