ArticleCell death & disease2023
Dual inhibition of thioredoxin reductase and proteasome is required for auranofin-induced paraptosis in breast cancer cells.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Disulfidptosis: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- TrxR Inhibition and Nrf2-FOXO3 Modulation by Repurposed Drugs: A Redox Strategy to Reverse Cancer Multidrug Resistance.Drug development research · 2026Review
- Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.Redox biology · 2026Review
- Nanomedicine-powered redox homeostasis modulation: Disrupting antioxidant systems and inducing oxidative stress for precision tumor therapy.Materials today. Bio · 2026Review
- Inflammation and RONS Dysregulation by Redox Enzymes as Mechanistic Links in HIV-1-Cancer Comorbidity.Pathogens (Basel, Switzerland) · 2026Review
- Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy.Nature communications · 2026Article
- Monitoring in real time and far-red imaging of HNature chemical biology · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Evaluating the Antiproliferative Effects of Tri(2-Furyl)- and Triphenylphosphine-Gold(I) Pyridyl- and Pyrimidine-Thiolate Complexes.Biomolecules · 2026Article
- A cyclometalated iridium(III) complex induces paraptotic cell death via mitochondrial dysfunction and ER stress in triple-negative breast cancer cells.Frontiers in pharmacology · 2026Article
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- ChaC1-based drug screenings identify a synergistic lethal effect of auranofin and proteasome inhibitors in hepatocellular carcinoma cells.Cell death discovery · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Auranofin Induces ER Stress-Mediated Apoptosis, and Its Combination With Bortezomib Elicits Paraptosis-Like Cell Death in Malignant Canine Mammary Tumour Cells.Veterinary and comparative oncology · 2025Article
- Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Beyond gold: the chemoenhancing mechanism and therapeutic potential of auranofin in melanoma.Cancer biology & medicine · 2025Article
- Article
- Integrating Machine Learning and Bulk and Single-Cell RNA Sequencing to Decipher Diverse Cell Death Patterns for Predicting the Prognosis of Neoadjuvant Chemotherapy in Breast Cancer.International journal of molecular sciences · 2025Article
- Integrated Bioinformatic Analyses Reveal Thioredoxin as a Putative Marker of Cancer Stem Cells and Prognosis in Prostate Cancer.Cancer informatics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Auranofin (AF), a gold (I)-containing phosphine compound, is being investigated for oncological application as a repurposed drug. We show here that 4~5 µM AF induces paraptosis, a non-apoptotic cell death mode characterized by dilation of the endoplasmic reticulum (ER) and mitochondria, in breast cancer cells. Although the covalent inhibition of thioredoxin reductase (TrxR), an enzyme that critically controls intracellular redox homeostasis, is considered the primary mechanism of AF's anticancer activity, knockdown of TrxR1 did not induce paraptosis. Instead, both TrxR1 knockdown plus the proteasome inhibitor (PI), bortezomib (Bz), and 2 μM AF plus Bz induced paraptosis, thereby mimicking the effect of 5 μM AF. These results suggest that the paraptosis induced by 5 μM AF requires the inhibition of both TrxR1 and proteasome. We found that TrxR1 knockdown/Bz or subtoxic doses of AF and Bz induced paraptosis selectively in breast cancer cells, sparing non-transformed MCF10A cells, whereas 4~5 μM AF killed both cancer and MCF10A cells. GSH depletion was found to be more critical than ROS generation for the paraptosis induced by dual TrxR1/proteasome inhibition. In this process, the ATF4/CHAC1 (glutathione-specific gamma-glutamylcyclotransferase 1) axis leads to GSH degradation, contributing to proteotoxic stress possibly due to the accumulation of misfolded thiol-containing proteins. These results suggest that the paraptosis-inducing strategy of AF plus a PI may provide an effective therapeutic strategy against pro-apoptotic therapy-resistant cancers and reduce the potential side effects associated with high-dose AF.
Indexed as
Identifiers
What OpenQuestion holds
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.