ArticleOncoTargets and therapy2021
A Novel Biological Activity of the STAT3 Inhibitor Stattic in Inhibiting Glutathione Reductase and Suppressing the Tumorigenicity of Human Cervical Cancer Cells via a ROS-Dependent Pathway.
Article in OncoTargets and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Endometrial Cell Senescence and Recurrent Spontaneous Abortion: Biomarker Potential of UCP2 and GSR.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- [Therapeutic mechanism of hederagenin, an active component inNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- ANXA2 in cancer: aberrant regulation of tumour cell apoptosis and its immune interactions.Cell death discovery · 2025Review
- [An artificial neural network diagnostic model for scleroderma and immune cell infiltration analysis based on mitochondria-associated genes].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.Drug design, development and therapy · 2024Review
- Computational workflow for discovering small molecular binders for shallow binding sites by integrating molecular dynamics simulation, pharmacophore modeling, and machine learning: STAT3 as case study.Journal of computer-aided molecular design · 2023Article
- Reactive Oxygen Species: A Crosslink between Plant and Human Eukaryotic Cell Systems.International journal of molecular sciences · 2023Review
- Enzymatic Redox Properties and Cytotoxicity of Irreversible Nitroaromatic Thioredoxin Reductase Inhibitors in Mammalian Cells.International journal of molecular sciences · 2023Article
- Review
- Discovery of new STAT3 inhibitors as anticancer agents using ligand-receptor contact fingerprints and docking-augmented machine learning.RSC advances · 2023Article
- SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.Cell death & disease · 2023Article
- Lymphatic metastasis-associated circRNA‒miRNA‒mRNA network for exploring the pathogenesis and therapeutic target of triple negative breast cancer based on whole-transcriptome sequencing analysis: an experimental verification study.Journal of translational medicine · 2022Article
- CDC25C is a prognostic biomarker and correlated with mitochondrial homeostasis in pancreatic adenocarcinoma.Bioengineered · 2022Article
- LCS-1 inhibition of superoxide dismutase 1 induces ROS-dependent death of glioma cells and degradates PARP and BRCA1.Frontiers in oncology · 2022Article
- Identification and chemical profiling of anti-alcoholic liver disease biomarkers of ginseng Huang jiu using UPLC-Q-Orbitrap-HRMS and network pharmacology-based analyses.Frontiers in nutrition · 2022Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionGlutathione reductase (GSR) provides reduced glutathione (GSH) to maintain redox homeostasis. Inhibition of GSR disrupts this balance, resulting in cell damage, which benefits cancer therapy. However, the effect of GSR inhibition on the tumorigenicity of human cervical cancer is not fully understood. MATERIALS AND
methodsTissue microarray analysis was employed to determine GSR expression in cervical cancer tissues by immunohistochemical staining. Cell death was measured with PI/FITC-annexin V staining. mRNA levels were measured via quantitative RT-PCR. Protein expression was measured by Western blotting and flow cytometry.
resultsThe expression of GSR was increased in human cervical cancer tissues, as shown by immunohistochemical staining. GSR knockdown by RNA interference in human cervical cancer cell lines resulted in cell death, suggesting the ability of GSR to maintain cancer cell survival. The STAT3 inhibitor 6-nitrobenzo[b]thiophene 1,1-dioxide (Stattic) also inhibited the enzymatic activity of GSR and induced the death of cervical cancer cells. More importantly, Stattic decreased the growth of xenograft tumors formed by cervical cancer cells in nude mice. Mechanistically, tumor cell death induced by Stattic-mediated GSR inhibition was ROS-dependent, since the ROS scavengers GSH and N-acetyl cysteine (NAC) reversed the effect of Stattic. In contrast, pharmacological and molecular inhibition of
conclusionStattic inhibits the enzymatic activity of GSR and induces STAT3-independent but ROS-dependent death of cervical cancer cells, suggesting its potential application as a therapeutic agent for human cervical cancers.
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