ArticleOncotarget2016
N-acetylcysteine negatively regulates Notch3 and its malignant signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Diminished Estrogen Induced Mitochondrial Protection and Immunosuppressive Microenvironment in Gastric Cancer with Depression.Cancers · 2025Article
- Meloxicam Alleviates Oxidative Stress Through Nrf2/HO-1 Activation in Bovine Endometrial Epithelial Cells.Veterinary sciences · 2025Article
- Vorinostat Treatment of Gastric Cancer Cells Leads to ROS-Induced Cell Inhibition and a Complex Pattern of Molecular Alterations in Nrf2-Dependent Genes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- A disulfiram derivative against lung cancer via the Notch signaling pathway without neurotoxicity and hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Cysteamine affects skeletal development and impairs motor behavior in zebrafish.Frontiers in pharmacology · 2022Article
- N-acetyl-L-cysteine Improves the Developmental Competence of Bovine Oocytes and Embryos Cultured In Vitro by Attenuating Oxidative Damage and Apoptosis.Antioxidants (Basel, Switzerland) · 2021Article
- Cigarette Smoke Activates NOTCH3 to Promote Goblet Cell Differentiation in Human Airway Epithelial Cells.American journal of respiratory cell and molecular biology · 2021Article
- Antioxidant Antagonises Chemotherapeutic Drug Effect in Lung Cancer Cell Line A549.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling.Journal of experimental & clinical cancer research : CR · 2019Article
- Vitamin D deficiency causes insulin resistance by provoking oxidative stress in hepatocytes.Oncotarget · 2017Article
- CRISPR-Cas9 Mediated NOX4 Knockout Inhibits Cell Proliferation and Invasion in HeLa Cells.PloS one · 2017Article
- Redox-sensitive MAPK and Notch3 regulate fibroblast differentiation and activation: a dual role of ERK1/2.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch3 receptor is expressed in a variety of cancers and the excised active intracellular domain (N3ICD) initiates its signaling cascade. N-acetylcysteine (NAC) as an antioxidant has been implicated in cancer prevention and therapy. In this study, we demonstrated a negative regulation of Notch3 by NAC in cancer cells. HeLa cells treated with NAC exhibited a time- and concentration-dependent decrease in Notch3 levels and its downstream effectors Hes1 and HRT1 in a manner independent of f-secretase or glutathione. In contrast, NAC did not affect protein levels of Notch1, the full length Notch3 precursor, or ectopically expressed N3ICD. Although SOD, catalase and NAC suppressed reactive oxygen species in HeLa cells, the first two antioxidants did not impact on Notch3 levels. While the mRNA expression of Notch3 was not altered by NAC, functional inhibition of lysosome, but not proteasome, blocked the NAC-dependent reduction of Notch3 levels. Furthermore, results from Notch3 silencing and N3ICD overexpression demonstrated that NAC prevented malignant phenotypes through down-regulation of Notch3 protein in multiple cancer cells. In summary, NAC reduces Notch3 levels through lysosome-dependent protein degradation, thereby negatively regulates Notch3 malignant signaling in cancer cells. These results implicate a novel NAC treatment in sensitizing Notch3-expressing tumors.
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