ArticleThe Journal of biological chemistry2014
Novel synthetic biscoumarins target tumor necrosis factor-α in hepatocellular carcinoma in vitro and in vivo.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 73 citations in OpenAlex.
- Flavonoids as Dual Topoisomerase I and II Inhibitors: Mechanistic Insights and Emerging Anticancer Strategies.Chemistry & biodiversity · 2026Review
- Discovery of oxazine-linked pyrimidine as an inhibitor of breast cancer growth and metastasis by abrogating NF-κB activation.Frontiers in oncology · 2024Article
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- An updated review summarizing the anticancer potential of flavonoids via targeting NF-kB pathway.Frontiers in pharmacology · 2024Review
- Hypoxia signaling in hepatocellular carcinoma: Challenges and therapeutic opportunities.Cancer metastasis reviews · 2023Review
- Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- Trifluoromethyl-substituted 3,5-bis(arylidene)-4-piperidones as potential anti-hepatoma and anti-inflammation agents by inhibiting NF-кB activation.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways.Journal of hepatocellular carcinoma · 2021Review
- Anti-neoplastic Effect of Ginkgolide C through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2020Article
- Brusatol suppresses STAT3-driven metastasis by downregulating epithelial-mesenchymal transition in hepatocellular carcinoma.Journal of advanced research · 2020Article
- Identification of Target Genes Related to Sulfasalazine in Triple-Negative Breast Cancer Through Network Pharmacology.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells.Biotechnology reports (Amsterdam, Netherlands) · 2020Article
- The IκB Kinase Inhibitor ACHP Targets the STAT3 Signaling Pathway in Human Non-Small Cell Lung Carcinoma Cells.Biomolecules · 2019Article
- Fangchinoline, a Bisbenzylisoquinoline Alkaloid can Modulate Cytokine-Impelled Apoptosis via the Dual Regulation of NF-κB and AP-1 Pathways.Molecules (Basel, Switzerland) · 2019Article
- Evidence for the Involvement of the Master Transcription Factor NF-κB in Cancer Initiation and Progression.Biomedicines · 2018Review
- N-Substituted Pyrido-1,4-Oxazin-3-Ones Induce Apoptosis of Hepatocellular Carcinoma Cells by Targeting NF-κB Signaling Pathway.Frontiers in pharmacology · 2018Article
- Novel 1,3,4-Oxadiazole Induces Anticancer Activity by Targeting NF-κB in Hepatocellular Carcinoma Cells.Frontiers in oncology · 2018Article
- Endophytic Fungi-Alternative Sources of Cytotoxic Compounds: A Review.Frontiers in pharmacology · 2018Review
- Identification of Novel Class of Triazolo-Thiadiazoles as Potent Inhibitors of Human Heparanase and their Anticancer Activity.BMC cancer · 2017Article
- Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2.International journal of medical sciences · 2017Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF is a pleotropic cytokine known to be involved in the progression of several pro-inflammatory disorders. Many therapeutic agents have been designed to counteract the effect of TNF in rheumatoid arthritis as well as a number of cancers. In the present study we have synthesized and evaluated the anti-cancer activity of novel biscoumarins in vitro and in vivo. Among new compounds, BIHC was found to be the most cytotoxic agent against the HepG2 cell line while exhibiting less toxicity toward normal hepatocytes. Furthermore, BIHC inhibited the proliferation of various hepatocellular carcinoma (HCC) cells in a dose- and time-dependent manner. Subsequently, using in silico target prediction, BIHC was predicted as a TNF blocker. Experimental validation was able to confirm this hypothesis, where BIHC could significantly inhibit the recombinant mouse TNF-α binding to its antibody with an IC50 of 16.5 μM. Furthermore, in silico docking suggested a binding mode of BIHC similar to a ligand known to disrupt the native, trimeric structure of TNF, and also validated with molecular dynamics simulations. Moreover, we have demonstrated the down-regulation of p65 phosphorylation and other NF-κB-regulated gene products upon BIHC treatment, and on the phenotypic level the compound shows inhibition of CXCL12-induced invasion of HepG2 cells. Also, we demonstrate that BIHC inhibits infiltration of macrophages to the peritoneal cavity and suppresses the activity of TNF-α in vivo in mice primed with thioglycollate broth and lipopolysaccharide. We comprehensively validated the TNF-α inhibitory efficacy of BIHC in an inflammatory bowel disease mice model.
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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.