scholarly journals Effect of (−)-Epigallocatechin Gallate to Staphylococcal Enterotoxin A on Toxin Activity

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1867
Author(s):  
Yuko Shimamura ◽  
Mio Utsumi ◽  
Chikako Hirai ◽  
Ami Kurokawa ◽  
Toshiyuki Kan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epigallocatechin Gallate ◽  
Direct Interaction ◽  
Model Solution ◽  
Staphylococcal Enterotoxin ◽  
Hydroxyl Group ◽  
Staphylococcal Enterotoxin A ◽  
Toxic Activity ◽  
Alkaline Conditions

Staphylococcal enterotoxin A (SEA) functions both as superantigens that stimulate non-specific T cell proliferation as well as potent gastrointestinal toxins. We previously reported that (−)-epigallocatechin gallate (EGCG) binds to SEA. Therefore, the ability of EGCG to inhibit SEA toxin activity was examined. As a result, EGCG significantly decreased SEA-induced expression and production of interferon gamma (IFN-γ). In addition, EGCG inhibited SEA-induced spleen cell proliferation. To investigate the role of the galloyl group in EGCG on SEA cytotoxicity in more detail, the effect of the binding of a hydroxyl group at position 3 of the galloyl group in EGCG to SEA on SEA cytotoxicity was examined using two methylated EGCG. SEA cytotoxicity was significantly controlled in both (−)-3′′-Me-EGCG and (−)-4′′-Me-EGCG. These results suggest that EGCG inhibits toxic activity via direct interaction with SEA or without any interaction with SEA. The binding affinity between SEA and EGCG under in vivo conditions was examined using a model solution. Although after treatment under acidic and alkaline conditions, the presence of protein and the digestive tract model solution, EGCG still interacted with SEA. Our studies are the first to demonstrate the effect of the binding of EGCG to SEA on toxin activity.

scholarly journals Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1936 ◽  
Author(s):  
Aide Negri ◽  
Valeria Naponelli ◽  
Federica Rizzi ◽  
Saverio Bettuzzi
Keyword(s):  
Cell Proliferation ◽  
Green Tea ◽  
Histone Deacetylases ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Dna Methyltransferases ◽  
Biologically Active ◽  
Special Focus ◽  
Dependent Inhibition

Green tea is a beverage that is widely consumed worldwide and is believed to exert effects on different diseases, including cancer. The major components of green tea are catechins, a family of polyphenols. Among them, epigallocatechin-gallate (EGCG) is the most abundant and biologically active. EGCG is widely studied for its anti-cancer properties. However, the cellular and molecular mechanisms explaining its action have not been completely understood, yet. EGCG is effective in vivo at micromolar concentrations, suggesting that its action is mediated by interaction with specific targets that are involved in the regulation of crucial steps of cell proliferation, survival, and metastatic spread. Recently, several proteins have been identified as EGCG direct interactors. Among them, the trans-membrane receptor 67LR has been identified as a high affinity EGCG receptor. 67LR is a master regulator of many pathways affecting cell proliferation or apoptosis, also regulating cancer stem cells (CSCs) activity. EGCG was also found to be interacting directly with Pin1, TGFR-II, and metalloproteinases (MMPs) (mainly MMP2 and MMP9), which respectively regulate EGCG-dependent inhibition of NF-kB, epithelial-mesenchimal transaction (EMT) and cellular invasion. EGCG interacts with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which modulates epigenetic changes. The bulk of this novel knowledge provides information about the mechanisms of action of EGCG and may explain its onco-suppressive function. The identification of crucial signalling pathways that are related to cancer onset and progression whose master regulators interacts with EGCG may disclose intriguing pharmacological targets, and eventually lead to novel combined treatments in which EGCG acts synergistically with known drugs.

scholarly journals Raf-1 Physically Interacts with Rb and Regulates Its Function: a Link between Mitogenic Signaling and Cell Cycle Regulation

1998 ◽  
Vol 18 (12) ◽  
pp. 7487-7498 ◽  
Author(s):  
Sheng Wang ◽  
Richik N. Ghosh ◽  
Srikumar P. Chellappan
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Surface ◽  
Mammalian Cells ◽  
Direct Interaction ◽  
Physical Interaction ◽  
Proliferating Cells

ABSTRACT Cells initiate proliferation in response to growth factor stimulation, but the biochemical mechanisms linking signals received at the cell surface receptors to the cell cycle regulatory molecules are not yet clear. In this study, we show that the signaling molecule Raf-1 can physically interact with Rb and p130 proteins in vitro and in vivo and that this interaction can be detected in mammalian cells without overexpressing any component. The binding of Raf-1 to Rb occurs subsequent to mitogen stimulation, and this interaction can be detected only in proliferating cells. Raf-1 can inactivate Rb function and can reverse Rb-mediated repression of E2F1 transcription and cell proliferation efficiently. The region of Raf-1 involved in Rb binding spanned residues 1 to 28 at the N terminus, and functional inactivation of Rb required a direct interaction. Serum stimulation of quiescent human fibroblast HSF8 cells led to a partial translocation of Raf-1 into the nucleus, where it colocalized with Rb. Further, Raf-1 was able to phosphorylate Rb in vitro quite efficiently. We believe that the physical interaction of Raf-1 with Rb is a vital step in the growth factor-mediated induction of cell proliferation and that Raf-1 acts as a direct link between cell surface signaling cascades and the cell cycle machinery.

scholarly journals SNHG9 Promotes the Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis

2021 ◽  
Author(s):  
Ramesh Bhandari ◽  
Sun Gui Feng ◽  
Liu Ya ◽  
Bian Zhixuan ◽  
Pan Quihui ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Pearson Correlation ◽  
Direct Interaction ◽  
Luciferase Reporter ◽  
Kaplan Meier ◽  
Rna Immunoprecipitation ◽  
Cellular Apoptosis

Abstract Background: Hepatoblastoma is common hepatic tumors occurring children between 0 – 5 years. Accumulating studies has shown lncRNA potential role in distinct cancers progression and development including the hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated the progression of distinct human cancers but, it`s specific molecular mechanisms in hepatoblastoma not unknown. Methods:In this study, we estimated SNHG9 expression on hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated the SNHG9 expression in hepatoblastoma cell lines and then determined the cell proliferation (CCK-8), colony formation, cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pulls down and Spemann’s Pearson correlation coefficient assay were performed to establish the interaction between the SNHG9, WNt3a and miR-23a-5p. Xenograft in-vivo tumorgenicity test was performed to elucidate therole of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drugs resistance in hepatoblastoma was also determined. Results:SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogeneic while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. In Xenograft tumorgenicity test showed SNHG9 downregulation significantly reduced the tumor growth on mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma.Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.

scholarly journals Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 609
Author(s):  
Yuko Shimamura ◽  
Rina Noaki ◽  
Ami Kurokawa ◽  
Mio Utsumi ◽  
Chikako Hirai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epigallocatechin Gallate ◽  
Staphylococcal Enterotoxin ◽  
Mouse Spleen ◽  
Staphylococcal Enterotoxin A ◽  
Spleen Cells ◽  
Gp130 Receptor ◽  
Stat Signaling ◽  
Ifn Γ ◽  
Phosphorylated Stat3

Staphylococcal enterotoxin A (SEA), which is a superantigen toxin protein, binds to cytokine receptor gp130. Gp130 activates intracellular signaling pathways, including the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The effects of SEA on the JAK/STAT signaling pathway in mouse spleen cells were examined. After treatment with SEA, mRNA expression levels of interferon gamma (IFN-γ) and suppressor of cytokine-signaling 1 (SOCS1) increased. SEA-induced IFN-γ and SOCS1 expression were decreased by treatment with (−)-epigallocatechin gallate (EGCG). The phosphorylated STAT3, Tyr705, increased significantly in a SEA concentration-dependent manner in mouse spleen cells. Although (−)-3″-Me-EGCG did not inhibit SEA-induced phosphorylated STAT3, EGCG and (−)-4″-Me-EGCG significantly inhibited SEA-induced phosphorylated STAT3. It was thought that the hydroxyl group at position 3 of the galloyl group in the EGCG was responsible for binding to SEA and suppressing SEA-induced phosphorylation of STAT3. Through protein thermal shift assay in vitro, the binding of the gp130 receptor to SEA and the phosphorylation of STAT3 were inhibited by the interaction between EGCG and SEA. As far as we know, this is the first report to document that EGCG inhibits the binding of the gp130 receptor to SEA and the associated phosphorylation of STAT3.

Immobilized Staphylococcal Enterotoxin A Is Sufficient to Induce T Cell Proliferation

1993 ◽  
Vol 151 (2) ◽  
pp. 467-473 ◽  
Author(s):  
Chantal J.J. Rust ◽  
Frits Koning ◽  
Wim C.A. van Schooten
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Staphylococcal Enterotoxin ◽  
T Cell Proliferation ◽  
Staphylococcal Enterotoxin A

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

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