Epigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathway

Zhang, Zhuoxian; Zhu, Qiuming; Wang, Siya; Shi, Chao

doi:10.1007/s11010-022-04550-w

Cited by 15 publications

(8 citation statements)

References 37 publications

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“…However, the possible mechanisms behind this were not revealed, until one scholar explained this inhibitory effect of EGCG on neutrophils depends on the strong interactions between EGCG and CD11b expressed on the neutrophil surface, which competitively suppresses the binding of specific molecules to the CD11b and particularly leads to a markedly reduced ability of neutrophils to bind intercellular adhesion molecule 1 (ICAM-1), an adhesion molecule mediating the passage of neutrophils through endothelial cells ( 106 ). Additionally, a recent report illuminated EGCG blocked NET formation as well as STAT3 and CXCL8 expression in the colon cancer-derived TANs, thereby inhibiting the invasion and migration of colon tumor ( 107 ). Briefly, the blocking of CD11b/ICAM-1 signal and inhibition of STAT3/CXCL8 pathway may be the key mechanisms by which EGCG suppresses neutrophil migration and infiltration into the TME.…”

Section: Immunomodulatory Roles In Immune Cells In Tmementioning

confidence: 99%

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Li,

Cao,

Sun

et al. 2024

Front. Immunol.

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Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

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Section: Immunomodulatory Roles In Immune Cells In Tmementioning

confidence: 99%

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Li,

Cao,

Sun

et al. 2024

Front. Immunol.

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“…Our results highlight STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets for Brevilin A’s anticancer activity. STAT3, a transcription factor integral to diverse biological processes, including cell proliferation, survival, differentiation, and angiogenesis [ 37 ], has been implicated in various human cancers, such as head and neck tumors, cervical cancer, gastric carcinoma, and colon cancer [ 38 – 41 ]. Notably, exosome-mediated transfer of specific microRNAs has been associated with the activation of STAT3 signaling-induced epithelial-mesenchymal transition in lung cancer cells [ 42 ].…”

Section: Disscussionmentioning

confidence: 99%

Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer

Wang,

Gao,

et al. 2024

BMC Complement Med Ther

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Background Traditional Chinese medicine (TCM) has been found widespread application in neoplasm treatment, yielding promising therapeutic candidates. Previous studies have revealed the anti-cancer properties of Brevilin A, a naturally occurring sesquiterpene lactone derived from Centipeda minima (L.) A.Br. (C. minima), a TCM herb, specifically against lung cancer. However, the underlying mechanisms of its effects remain elusive. This study employs network pharmacology and experimental analyses to unravel the molecular mechanisms of Brevilin A in lung cancer. Methods The Batman-TCM, Swiss Target Prediction, Pharmmapper, SuperPred, and BindingDB databases were screened to identify Brevilin A targets. Lung cancer-related targets were sourced from GEO, Genecards, OMIM, TTD, and Drugbank databases. Utilizing Cytoscape software, a protein-protein interaction (PPI) network was established. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), and gene-pathway correlation analysis were conducted using R software. To validate network pharmacology results, molecular docking, molecular dynamics simulations, and in vitro experiments were performed. Results We identified 599 Brevilin A-associated targets and 3864 lung cancer-related targets, with 155 overlapping genes considered as candidate targets for Brevilin A against lung cancer. The PPI network highlighted STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets. GO and KEGG analyses revealed 2893 enriched GO terms and 157 enriched KEGG pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. GSEA demonstrated a close association between hub genes and lung cancer. Gene-pathway correlation analysis indicated significant associations between hub genes and the cellular response to hypoxia pathway. Molecular docking and dynamics simulations confirmed Brevilin A’s interaction with PTEN and HIF1A, respectively. In vitro experiments demonstrated Brevilin A-induced dose- and time-dependent cell death in A549 cells. Notably, Brevilin A treatment significantly reduced HIF-1α mRNA expression while increasing PTEN mRNA levels. Conclusions This study demonstrates that Brevilin A exerts anti-cancer effects in treating lung cancer through a multi-target and multi-pathway manner, with the HIF pathway potentially being involved. These results lay a theoretical foundation for the prospective clinical application of Brevilin A.

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“…Fangchinoline increases oxidative stress to suppress STAT3 signaling to reduce myeloma progression [ 58 ]. Moreover, epigallocatechin-3-gallate decreases STAT3 expression by impairing colon tumor cell invasion and metastasis [ 59 ]. According to these descriptions, the function of STAT3 signaling in cancer is oncogenic and its suppression may therefore introduce new therapeutics for tumor therapy.…”

Section: Stat3 Signaling: An Overviewmentioning

confidence: 99%

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

et al. 2023

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Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial–mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC. Graphical Abstract

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Epigallocatechin-3-gallate inhibits the formation of neutrophil extracellular traps and suppresses the migration and invasion of colon cancer cells by regulating STAT3/CXCL8 pathway

Cited by 15 publications

References 37 publications

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

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