Inhibitory Effects of Epigallocatechin-3 Gallate, a catechin in Green Tea, on Tumor-Associated Endothelial Cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 21890006
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: OHGA Noritaka Hokkaido University, 大学院・歯学研究科, 特任助教 (40548202)
• Project Period (FY): 2009 – 2010
• Keywords: 緑茶カテキン / 腫瘍血管新生 / 血管内皮前駆細胞 / 血管新生阻害薬

Research Abstract

The epigallocatechin-3 gallate (EGCG) in green tea suppresses tumor growth, but it is not known whether it specifically inhibits tumor angiogenesis. We examined the anti-angiogenic effect of EGCG on tumor-associated endothelial cells (TECs), EPCs, and normal endothelial cells (NECs). TECs were isolated and cultured from human tumor xenografts in nude mice. EGCG suppressed the migration of TECs and EPCs. EGCG also inhibited the phosphorylation of Akt in EPCs. MMP-9 in the bone marrow is involved in mobilizing bone marrow-derived VEGFR-2 positive cells into peripheral circulation. Expression of MMP-9 mRNA was suppressed in bone marrow stromal cells by EGCG. In vivo model, EGCG reduced melanoma growth. Our study showed that EGCG has anti-angiogenic effects. EGCG is a promising angiogenesis inhibitor for cancer therapy.

Research Products

• [Journal Article] Cyclooxygenase-2 inhibition causes antiangiogenic effects on tumor endothelial and vascular progenitor cells (2011)
  • Author(s): Muraki C., Ohga N., Hida Y., Nishihara H., Kato Y., Tsuchiya K., Matsuda K., Totsuka Y., Shindoh M., Hida K.
  • Journal Title: Int J Cancer (in press)
  • Peer Reviewed
• [Journal Article] HuR keeps an angiogenic switch on by stabilizing mRNA of VEGF and COX-2 in tumor endothelium (2011)
  • Author(s): Kurosu T., Ohga N., Hida Y., Maishi N., Akiyama K., Kakuguchi W., Kuroshima T., Kondo M., Akino T., Totsuka Y., Shindoh M., Higashino F., Hida K.
  • Journal Title: Br J Cancer 104(5) Pages: 819-829
  • Peer Reviewed
• [Journal Article] Crosstalk between blood vessels and tumor microenvironment (2010)
  • Author(s): Hida K., Ohga N., Kurosu T., Totsuka Y., Shindoh M.
  • Journal Title: Oral Sci Int 7(1) Pages: 1-10
  • Peer Reviewed
• [Journal Article] Isolation and Culture of Microvascular Endothelial Cells from Murine Inguinal and Epididymal Adipose Tissue (2010)
  • Author(s): Kajimoto K., Hossen MN., Hida K., Ohga N., Akita H., Hyodo M., Hida Y., Harashima H.
  • Journal Title: J Immunol Methods 357(1-2) Pages: 43-50
  • Peer Reviewed
• [Journal Article] Isolated tumor endothelial cells maintain specific character during long-term culture (2010)
  • Author(s): Matsuda K., Ohga N., Hida Y., Muraki C., Kurosu T., Tsuchiya K., Akino T., Shih SC, Totsuka Y., Klagsbrun M., Shindoh M., Hida K.
  • Journal Title: Biochem Biophys Res Commun 394 Pages: 947-954
  • Peer Reviewed
• [Journal Article] BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo (2010)
  • Author(s): Suzuki Y., Ohga N., Morishita Y., Hida K., Miyazono K., Watabe T.
  • Journal Title: J Cell Sci 123(10) Pages: 1684-1692
  • Peer Reviewed
• [Journal Article] Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization (2010)
  • Author(s): Tsuchiya K., Hida K., Hida Y., Muraki C., Ohga N., Kondo T., Miseki T., Nakagawa K, Shindoh M., Harabayashi T., Shinohara N,, Nonomura K., Kobayashi M.
  • Journal Title: Int J Oncol 36(6) Pages: 1379-1386
  • Peer Reviewed
• [Journal Article] Significance of Antiangiogenic Therapy in Head and Neck Cancer-Heterogeneity of Tumor Endothelium. (2009)
  • Author(s): Hida K., Ohga N., Hida Y., Shindoh M.
  • Journal Title: Jpn Dent Sci Review 46 Pages: 26-32
  • Peer Reviewed
• [Journal Article] Inhibitory Effects of Epigallocatechin-3 Gallate, a Polyphenol in Green Tea, on Tumor-Associated Endothelial Cells and Endothelial Progenitor Cells. (2009)
  • Author(s): Ohga N., Hida K., Hida Y., Muraki C., Tsuchiya K., Matsuda K., Ohiro Y., Totsuka Y., Shindoh M.
  • Journal Title: Cancer Sci 100(10) Pages: 1963-1970
  • Peer Reviewed
• [Presentation] 緑茶カテキンEGCGは腫瘍血管内皮細胞ならびに血管内皮前駆細胞に対する抑制効果を有する (2010)
  • Author(s): 大賀則孝
  • Organizer: 第64回日本口腔科学会学術集会
  • Place of Presentation: 札幌プリンスホテル(札幌)
  • Year and Date: 2010-06-24
• [Presentation] 緑茶ポリフェノールは腫瘍血管内皮細胞と血管内皮前駆細胞に対する抑制抗効果を有する (2009)
  • Author(s): 大賀則孝
  • Organizer: 第54回日本口腔外科学会総会・学術大会
  • Place of Presentation: 札幌コンベンションセンター(札幌)
  • Year and Date: 2009-10-09
• [Presentation] 緑茶ポリフェノールEGCGは腫瘍血管内皮に対する制御効果を有する (2009)
  • Author(s): 大賀則孝
  • Organizer: 第17回日本血管生物医学会
  • Place of Presentation: 東京大学安田講堂(東京)
  • Year and Date: 2009-10-09
• [Presentation] 緑茶ポリフェノールEGCGは腫瘍血管内皮に対する制御効果を有する (2009)
  • Author(s): 大賀則孝
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-02
• [Remarks] ホームページ等
  • URL: http://www.den.hokudai.ac.jp/vascular-biology.com/
• [Patent(Industrial Property Rights)] 腫瘍血管新生阻害剤 (2010)
  • Inventor(s): 樋田京子、樋田泰浩、大賀則孝
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 特許出願,特願2010-062825
  • Filing Date: 2010-03-10
• [Patent(Industrial Property Rights)] 腫瘍血管新生阻害剤 (2010)
  • Inventor(s): 樋田京子、樋田泰浩、大賀則孝
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 特許出願,特願2010-062831
  • Filing Date: 2010-03-10