Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December 2013 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December 2013 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Mechanism of the inhibition of the STAT3 signaling pathway by EGCG

  • Authors:
    • Yang Wang
    • Xuequn Ren
    • Chaoyang Deng
    • Lu Yang
    • Erfu Yan
    • Tao Guo
    • Yanmin Li
    • Marvin Xuejun Xu
  • View Affiliations / Copyright

    Affiliations: Huaihe Hospital, Henan University, Kaifeng 475000, P.R. China, Shanghai McAry Biomedical Technology Co. Ltd., Zhangjiang Hi-Tech Park, Pudong New Area, Shanghai 201203, P.R. China, Department of Pharmacy, Tianjin University, Tianjin, P.R. China, Center for Drug Delivery System, Shanghai Institute of Materia Medica, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai 201203, P.R. China, Department of Physics, Shangqiu Normal College, Shangqiu 476000, P.R. China, Department of Pharmacology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
  • Pages: 2691-2696
    |
    Published online on: September 20, 2013
       https://doi.org/10.3892/or.2013.2743
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Signal transducer and activator of transcription 3 (STAT3) is an oncogene that promotes cell survival, proliferation, and motility. In the present study, we explored the mechanism involved in the inhibition by epigallocatechin-3-gallate (EGCG) of STAT3 signaling as detected by surface plasmon resonance (SPR)-binding assays and in silico docking. Stat3‑binding assay indicated that EGCG significantly interrupted Stat3 peptide binding at micromolar concentrations, and the docking experiments indicated that EGCG had a strong interaction with Arg-609, one of the key residues in the STAT3 SH2 domain that contributes greatly to Stat3 and phosphorylated peptide binding. Following treatment of the hepatocellular carcinoma cell lines BEL-7402 and QGY-7703 with EGCG, in vitro, EGCG significantly suppressed cell proliferation as detected by MTT assay, induced apoptosis as detected by flow cytometry, dramatically lowered the expression levels of phosphorylated Stat3 proteins (p-Stat3) as determined by immunoblot detection, and inhibited the expression of multiple genes including Bcl-xL, c-Myc, VEGF and cyclin D1 as demonstrated by RT-PCR analysis. In conclusion, our research data indicate that the anticancer function of green tea results from the inhibition of the STAT3 signaling pathway by EGCG.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Darnell JE Jr, Kerr IM and Stark GR: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 264:1415–1421. 1994. View Article : Google Scholar : PubMed/NCBI

2 

Buettner R, Mora LB and Jove R: Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res. 8:945–954. 2002.PubMed/NCBI

3 

Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, Sung B and Ichikawa H: Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann NY Acad Sci. 1091:151–169. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Redell MS and Tweardy DJ: Targeting transcription factors in cancer: challenges and evolving strategies. Drug Discov Today Technol. 3:261–267. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Whittaker S, Marais R and Zhu AX: The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene. 29:4989–5005. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Berishaj M, Gao SP, Ahmed S, Leslie K, Al-Ahmadie H, Gerald WL, Bornmann W and Bromberg JF: Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer. Breast Cancer Res. 9:R322007. View Article : Google Scholar : PubMed/NCBI

7 

Lin L, Amin R, Gallicano GI, Glasgow E, Jogunoori W, Jessup JM, Zasloff M, Marshall JL, Shetty K, Johnson L, Mishra L and He AR: The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-β signaling. Oncogene. 28:961–972. 2009.PubMed/NCBI

8 

Soresi M, Giannitrapani L, D’Antona F, Florena AM, La Spada E, Terranova A, Cervello M, D’Alessandro N and Montalto G: Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma. World J Gastroenterol. 12:2563–2568. 2006.PubMed/NCBI

9 

Berasin C, Castillo J, Perugorria MJ, Latasa MU, Prieto J and Avila MA: Inflammation and liver cancer: new molecular links. Ann NY Acad Sci. 1155:206–221. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, Factor VM and Thorgeirsson SS: Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 130:1117–1128. 2006. View Article : Google Scholar : PubMed/NCBI

11 

To KF, Chan MW, Leung WK, Ng EK, Yu J, Bai AH, Lo AW, Chu SH, Tong JH, Lo KW, Sung JJ and Chan FK: Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line. Br J Cancer. 91:1335–1341. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Li HC, Yashiki S, Sonoda J, Lou H, Ghosh SK, Byrnes JJ, Lema C, Fujiyoshi T, Karasuyama M and Sonoda S: Green tea polyphenoles induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Jpn J Cancer Res. 91:34–40. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Park G, Yoon BS, Moon JH, Kim B, Jun EK, Oh S, Kim H, Song HJ, Noh JY, Oh C and You S: Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway. J Invest Dermatol. 128:2429–2441. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Ahn HY, Hadizadeh KR, Seul C, Yun YP, Vetter H and Sachinidis A: Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells. Mol Biol Cell. 10:1093–1104. 1999. View Article : Google Scholar

15 

Xu X, Kasembeli MM, Jiang X, Tweardy BJ and Tweardy DJ: Chemical probes that competitively and selectively inhibit Stat3 activation. PLoS One. 4:e47832009. View Article : Google Scholar : PubMed/NCBI

16 

Kasembeli MM, Xu X and Tweardy DJ: SH2 domain binding to phosphopeptide ligands: potential for drug targeting. Front Biosci. 14:1010–1022. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Shao H, Xu X, Jing N and Tweardy DJ: Unique structural determinants for Stat3 recruitment and activation by the granulocyte colony-stimulating factor receptor at phosphotyrosine ligands 704 and 744. J Immunol. 176:2933–2941. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Shao H, Xu X, Mastrangelo MA, Jing N, Cook RG, Legge GB and Tweardy DJ: Structural requirements for signal transducer and activator of transcription 3 binding to phosphotyrosine ligands containing the YXXQ motif. J Biol Chem. 279:18967–18973. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Takada M, Nakamura Y, Koizumi T, Toyama H, Kamigaki T, Suzuki Y, Takeyama Y and Kuroda Y: Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate. Pancreas. 25:45–48. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Zhu B, Chen H, Zhan W, Wang CY, Cai SR, Wang Z, Zhang CH and He YL: (−)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer. World J Gastroenterol. 7:2315–2325. 2011.

21 

Yang GY, Liao J, Kim K, Yurkow EJ and Yang CS: Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 19:611–616. 1998. View Article : Google Scholar : PubMed/NCBI

22 

Yang CS, Lambert JD, Hou Z, Ju J, Lu G and Hao X: Molecular targets for the cancer preventive activity of tea polyphenols. Mol Carcinog. 45:431–435. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Shankar S, Suthakar G and Srivastava RK: Epigallocatechin-3-gallate inhibits cell cycle and induces apoptosis in pancreatic cancer. Front Biosci. 12:5039–5051. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Ren X, Deng C, Yang L, Yan E, Guo T, Li Y and Xu MX: Mechanism of the inhibition of the STAT3 signaling pathway by EGCG. Oncol Rep 30: 2691-2696, 2013.
APA
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T. ... Xu, M.X. (2013). Mechanism of the inhibition of the STAT3 signaling pathway by EGCG. Oncology Reports, 30, 2691-2696. https://doi.org/10.3892/or.2013.2743
MLA
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T., Li, Y., Xu, M. X."Mechanism of the inhibition of the STAT3 signaling pathway by EGCG". Oncology Reports 30.6 (2013): 2691-2696.
Chicago
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T., Li, Y., Xu, M. X."Mechanism of the inhibition of the STAT3 signaling pathway by EGCG". Oncology Reports 30, no. 6 (2013): 2691-2696. https://doi.org/10.3892/or.2013.2743
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Ren X, Deng C, Yang L, Yan E, Guo T, Li Y and Xu MX: Mechanism of the inhibition of the STAT3 signaling pathway by EGCG. Oncol Rep 30: 2691-2696, 2013.
APA
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T. ... Xu, M.X. (2013). Mechanism of the inhibition of the STAT3 signaling pathway by EGCG. Oncology Reports, 30, 2691-2696. https://doi.org/10.3892/or.2013.2743
MLA
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T., Li, Y., Xu, M. X."Mechanism of the inhibition of the STAT3 signaling pathway by EGCG". Oncology Reports 30.6 (2013): 2691-2696.
Chicago
Wang, Y., Ren, X., Deng, C., Yang, L., Yan, E., Guo, T., Li, Y., Xu, M. X."Mechanism of the inhibition of the STAT3 signaling pathway by EGCG". Oncology Reports 30, no. 6 (2013): 2691-2696. https://doi.org/10.3892/or.2013.2743
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team