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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2019 Volume 20 Issue 2

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
August-2019 Volume 20 Issue 2

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 Open Access

The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study

  • Authors:
    • Hitoshi Yoshimura
    • Hisato Yoshida
    • Shinpei Matsuda
    • Takashi Ryoke
    • Keiichi Ohta
    • Masahiro Ohmori
    • Satoshi Yamamoto
    • Tamotsu Kiyoshima
    • Motohiro Kobayashi
    • Kazuo Sano
  • View Affiliations / Copyright

    Affiliations: Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan, Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Fukuoka 812‑8582, Japan, Department of Tumor Pathology, Unit of Pathological Sciences, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan
    Copyright: © Yoshimura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1139-1148
    |
    Published online on: June 4, 2019
       https://doi.org/10.3892/mmr.2019.10331
  • 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

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the oral region. Despite current therapeutic strategies, the survival rate has not been improved for several decades. Thus, it is important to develop a novel approach for the treatment of OSCC. Epigallocatechin‑3‑gallate (EGCG) is a major constituent of green tea and has previously been demonstrated to inhibit the growth of several types of cancer cells. However, few studies have investigated the effect of EGCG on human OSCC cells, especially in experimental animal models. The aim of the present study was to evaluate the therapeutic potential of EGCG for targeting human OSCC in vitro and in vivo. In the in vitro experiments, EGCG suppressed HSC‑3 cell viability in a time‑ and dose‑dependent manner. Cell cycle analysis revealed that EGCG induced G1 phase arrest of the tumor cells. Apoptosis was examined by Annexin V and propidium iodide staining, assays of caspase‑3 and -7 activity and TdT‑mediated dUTP nick end labeling (TUNEL) staining. Treatment with EGCG significantly increased caspase‑3 and -7 activities, and the percentage of apoptotic cells when compared with control cells. In the in vivo xenograft experiment on mice, EGCG treatment resulted in a 45.2% reduction in tumor size as compared with the control group without weight loss. In vivo cell proliferation and apoptosis were assessed by immunohistochemical Ki‑67 staining and the TUNEL staining. There were significant differences in Ki‑67 expression between the EGCG treatment group and control group, and the percentage of apoptotic cells in the EGCG treatment group was significantly greater than that in the control group. These results indicated that EGCG significantly inhibited cell proliferation by affecting the cell cycle progression and apoptosis in vitro and in vivo. These findings suggest that EGCG may have clinical applications as a novel approach to oral‑cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Iriti M and Varoni EM: Chemopreventive potential of flavonoids in oral squamous cell carcinoma in human studies. Nutrients. 5:2564–2576. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Rivera C: Essentials of oral cancer. Int J Clin Exp Pathol. 8:11884–11894. 2015.PubMed/NCBI

4 

Schwartz JL, Baker V, Larios E and Chung FL: Molecular and cellular effects of green tea on oral cells of smokers: A pilot study. Mol Nutr Food Res. 49:43–51. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Wang B, Zhang S, Yue K and Wang XD: The recurrence and survival of oral squamous cell carcinoma: A report of 275 cases. Chin J Cancer. 32:614–618. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Chu C, Deng J, Man Y and Qu Y: Green tea extracts epigallocatechin-3-gallate for different treatments. Biomed Res Int. 2017:56156472017. View Article : Google Scholar : PubMed/NCBI

7 

Narotzki B, Reznick AZ, Aizenbud D and Levy Y: Green tea: A promising natural product in oral health. Arch Oral Biol. 57:429–435. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Imai K, Suga K and Nakachi K: Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 26:769–775. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Lecumberri E, Dupertuis YM, Miralbell R and Pichard C: Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin Nutr. 32:894–903. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE and Ellis LM: EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer. 84:844–850. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Urusova DV, Shim JH, Kim DJ, Jung SK, Zykova TA, Carper A, Bode AM and Dong Z: Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1. Cancer Prev Res (Phila). 4:1366–1377. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Yoshida H, Yoshimura H, Matsuda S, Ryoke T, Kiyoshima T, Kobayashi M and Sano K: Effects of peritumoral bevacizumab injection against oral squamous cell carcinoma in a nude mouse xenograft model: A preliminary study. Oncol Lett. 15:8627–8634. 2018.PubMed/NCBI

13 

Kim CS, Cho SH, Chun HS, Lee SY, Endou H, Kanai Y and Kim DK: BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells. Biol Pharm Bull. 31:1096–1100. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Moon SM, Yun SJ, Kook JK, Kim HJ, Choi MS, Park BR, Kim SG, Kim BO, Lee SY, Ahn H, et al: Anticancer activity of Saussurea lappa extract by apoptotic pathway in KB human oral cancer cells. Pharm Biol. 51:1372–1377. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Scholzen T and Gerdes J: The Ki-67 protein: From the known and the unknown. J Cell Physiol. 182:311–322. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Sinevici N and O'Sullivan J: Oral cancer: Deregulated molecular events and their use as biomarkers. Oral Oncol. 61:12–18. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Singh BN, Shankar S and Srivastava RK: Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochem Pharmacol. 82:1807–1821. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Elattar TM and Virji AS: Effect of tea polyphenols on growth of oral squamous carcinoma cells in vitro. Anticancer Res. 20:3459–3465. 2000.PubMed/NCBI

19 

Masuda M, Suzui M and Weinstein IB: Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res. 7:4220–4229. 2001.PubMed/NCBI

20 

Hengartner MO: The biochemistry of apoptosis. Nature. 407:770–776. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Kaufmann SH and Earnshaw WC: Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 256:42–49. 2000. View Article : Google Scholar : PubMed/NCBI

22 

Lin HY, Hou SC, Chen SC, Kao MC, Yu CC, Funayama S, Ho CT and Way TD: (−)-Epigallocatechin gallate induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling in head and neck squamous cell carcinoma cells. J Agric Food Chem. 60:2480–2489. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Cohen GM: Caspases: The executioners of apoptosis. Biochem J. 326:1–16. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Yamamoto T, Hsu S, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Lockwood P, Ueta E, Osaki T and Schuster G: Green tea polyphenol causes differential oxidative environments in tumor versus normal epithelial cells. J Pharmacol Exp Ther. 307:230–236. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Chen D, Milacic V, Chen MS, Wan SB, Lam WH, Huo C, Landis-Piwowar KR, Cui QC, Wali A, Chan TH and Dou QP: Tea polyphenols, their biological effects and potential molecular targets. Histol Histopathol. 23:487–496. 2008.PubMed/NCBI

26 

Mery B, Rancoule C, Guy JB, Espenel S, Wozny AS, Battiston-Montagne P, Ardail D, Beuve M, Alphonse G, Rodriguez-Lafrasse C and Magné N: Preclinical models in HNSCC: A comprehensive review. Oral Oncol. 65:51–56. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Chen PN, Chu SC, Kuo WH, Chou MY, Lin JK and Hsieh YS: Epigallocatechin-3 gallate inhibits invasion, epithelial-mesenchymal transition, and tumor growth in oral cancer cells. J Agric Food Chem. 59:3836–3844. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Chang YC, Chen PN, Chu SC, Lin CY, Kuo WH and Hsieh YS: Black tea polyphenols reverse epithelial-to-mesenchymal transition and suppress cancer invasion and proteases in human oral cancer cells. J Agric Food Chem. 60:8395–8403. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Hwang YS, Park KK and Chung WY: Epigallocatechin-3 gallate inhibits cancer invasion by repressing functional invadopodia formation in oral squamous cell carcinoma. Eur J Pharmacol. 715:286–295. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Yang CS and Wang X: Green tea and cancer prevention. Nutr Cancer. 62:931–937. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Yang CS, Sang S, Lambert JD and Lee MJ: Bioavailability issues in studying the health effects of plant polyphenolic compounds. Mol Nutr Food Res. 52 (Suppl 1):S139–S151. 2008.PubMed/NCBI

32 

Sheth SH, Johnson DE, Kensler TW and Bauman JE: Chemoprevention targets for tobacco-related head and neck cancer: Past lessons and future directions. Oral Oncol. 51:557–564. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yoshimura H, Yoshida H, Matsuda S, Ryoke T, Ohta K, Ohmori M, Yamamoto S, Kiyoshima T, Kobayashi M, Sano K, Sano K, et al: The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study. Mol Med Rep 20: 1139-1148, 2019.
APA
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M. ... Sano, K. (2019). The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study. Molecular Medicine Reports, 20, 1139-1148. https://doi.org/10.3892/mmr.2019.10331
MLA
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M., Yamamoto, S., Kiyoshima, T., Kobayashi, M., Sano, K."The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study". Molecular Medicine Reports 20.2 (2019): 1139-1148.
Chicago
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M., Yamamoto, S., Kiyoshima, T., Kobayashi, M., Sano, K."The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study". Molecular Medicine Reports 20, no. 2 (2019): 1139-1148. https://doi.org/10.3892/mmr.2019.10331
Copy and paste a formatted citation
x
Spandidos Publications style
Yoshimura H, Yoshida H, Matsuda S, Ryoke T, Ohta K, Ohmori M, Yamamoto S, Kiyoshima T, Kobayashi M, Sano K, Sano K, et al: The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study. Mol Med Rep 20: 1139-1148, 2019.
APA
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M. ... Sano, K. (2019). The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study. Molecular Medicine Reports, 20, 1139-1148. https://doi.org/10.3892/mmr.2019.10331
MLA
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M., Yamamoto, S., Kiyoshima, T., Kobayashi, M., Sano, K."The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study". Molecular Medicine Reports 20.2 (2019): 1139-1148.
Chicago
Yoshimura, H., Yoshida, H., Matsuda, S., Ryoke, T., Ohta, K., Ohmori, M., Yamamoto, S., Kiyoshima, T., Kobayashi, M., Sano, K."The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In vitro and in vivo murine xenograft study". Molecular Medicine Reports 20, no. 2 (2019): 1139-1148. https://doi.org/10.3892/mmr.2019.10331
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