ArticleRedox biology2020
Downregulation of thioredoxin-1-dependent CD95 S-nitrosation by Sorafenib reduces liver cancer.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
What it found
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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.
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
11 citing papers in PubMed, 20 citations in OpenAlex.
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Article
- The Importance of Thioredoxin-1 in Health and Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Inhibitory Peptide of Soluble Guanylyl Cyclase/Trx1 Interface Blunts the Dual Redox Signaling Functions of the Complex.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- The Nrf2 Pathway in Liver Diseases.Frontiers in cell and developmental biology · 2022Review
- The Role of the BH4 Cofactor in Nitric Oxide Synthase Activity and Cancer Progression: Two Sides of the Same Coin.International journal of molecular sciences · 2021Review
- Antioxidants Threaten Multikinase Inhibitor Efficacy against Liver Cancer by Blocking Mitochondrial Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Article
- Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation.Molecules (Basel, Switzerland) · 2021Review
- Efficacy of Sorafenib Combined with Interventional Therapy on Primary Liver Cancer Patients and Its Effect on Serum AFP, VEGF, and GGT.Journal of oncology · 2021Article
- The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) represents 80% of the primary hepatic neoplasms. It is the sixth most frequent neoplasm, the fourth cause of cancer-related death, and 7% of registered malignancies. Sorafenib is the first line molecular targeted therapy for patients in advanced stage of HCC. The present study shows that Sorafenib exerts free radical scavenging properties associated with the downregulation of nuclear factor E2-related factor 2 (Nrf2)-regulated thioredoxin 1 (Trx1) expression in liver cancer cells. The experimental downregulation and/or overexpression strategies showed that Trx1 induced activation of nitric oxide synthase (NOS) type 3 (NOS3) and S-nitrosation (SNO) of CD95 receptor leading to an increase of caspase-8 activity and cell proliferation, as well as reduction of caspase-3 activity in liver cancer cells. In addition, Sorafenib transiently increased mRNA expression and activity of S-nitrosoglutathione reductase (GSNOR) in HepG2 cells. Different experimental models of hepatocarcinogenesis based on the subcutaneous implantation of HepG2 cells in nude mice, as well as the induction of HCC by diethylnitrosamine (DEN) confirmed the relevance of Trx1 downregulation during the proapoptotic and antiproliferative properties induced by Sorafenib. In conclusion, the induction of apoptosis and antiproliferative properties by Sorafenib were related to Trx1 downregulation that appeared to play a relevant role on SNO of NOS3 and CD95 in HepG2 cells. The transient increase of GSNOR might also participate in the deactivation of CD95-dependent proliferative signaling in liver cancer cells.
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What Socratic 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 Socratic graph.