Targeting receptor tyrosine kinases for colon cancer chemoprevention by green tea catechin, EGCG

• Project/Area Number: 18790457
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: SHIMIZU Masahito Gifu University, 医学部附属病院, 助教授 (90402198)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,540,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: EGCG / RTK / 大腸癌 / 発癌予防 / RTM

Research Abstract

我々は本研究で、緑茶カテキンEGCGが、IGF/IGF1-Rの異常活性を阻害し、ヒト大腸および肝癌細胞の増殖を抑制すること、また肥満および炎症関連マウス大腸発癌を抑制することを明らかにした。さらに、緑茶抽出物であるGTEの補助投与が、内視鏡的切除術後の大腸腺腫の異所性再発を有意に抑制することも明らかにした。今回の研究結果は、EGCGや他の緑茶抽出物を用いた大腸および肝発癌予防の可能性を示唆するものと考えられた。

Research Products

• [Journal Article] EGCG inhibits activation of the insulin-like growth factor (IGF)/IGF-1 receptor axis in human hepatocellular carcinoma cells (2008)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Tatebe H, Nakagawa T, Hara Y, Weinstein IB, Moriwaki H
  • Journal Title: Cancer Lett 262 Pages: 10-18
  • Peer Reviewed
• [Journal Article] Synergistic growth inhibition by 9-cis-retinoic acid plus trastuzumab in human hepatocellular carcinoma cells (2008)
  • Author(s): Tatebe H, Shimizu M, Shirakami Y, Tsurumi H, Moriwaki H
  • Journal Title: Clin Cancer Res 14 Pages: 2806-2812
  • Peer Reviewed
• [Journal Article] EGCG and Polyphenon E attenuate inflammation-related mouse colon carcinogenesis induced by AOM plus DDS (2008)
  • Author(s): Shirakami Y, Shimizu M, Tsurumi H, Hara Y, Tanaka T, Moriwaki H
  • Journal Title: Mol Med Rep 1 Pages: 355-361
  • NAID: 120006340759
  • Peer Reviewed
• [Journal Article] (-)-Epigallocatechin gallate suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJ- db/db mice (2008)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Adachi S, Hata K, Hirose Y, Tsurumi H, et al
  • Journal Title: Cancer Prev Res 1 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Targeting Receptor Tyrosine kinases for chemoprevention by green tea catechin, EGCG (2008)
  • Author(s): Shimizu M, Shirakami Y, Moriwaki H
  • Journal Title: Int J Mol Sci 9 Pages: 1034-1049
  • NAID: 120006341903
  • Peer Reviewed
• [Journal Article] Synergistic effects of PPARgamma ligands and retinoids in cancer treatment (2008)
  • Author(s): Shimizu M, Moriwaki H
  • Journal Title: PPAR Res 2008 181047 (Online, Open access journal)
  • Peer Reviewed
• [Journal Article] Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study (2008)
  • Author(s): Shimizu M, Fukutomi Y, Ninomiya M, Nagura K, Kato T, Araki H, Suganuma M, Fujiki H, Moriwaki H
  • Journal Title: Cancer Epidemiol Biomarkers Prev 17 Pages: 3020-3025
  • Peer Reviewed
• [Journal Article] Maxfield FR, Weinstein IB. (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells (2008)
  • Author(s): Adachi S, Nagao T, To S, Joe AK, Shimizu M, Matsushima-Nishiwaki R, Kozawa O, Moriwaki H
  • Journal Title: Carcinogenesis 29 Pages: 1986-1993
  • Peer Reviewed
• [Journal Article] EGCG inhibits activation of the insulin-like growth factor (IGF)/IGF-1 receptor axis in human hepatocellular carcinoma cells (2008)
  • Author(s): Shimizu M, et.al.
  • Journal Title: Cancer Lett 262 Pages: 10-18
  • Peer Reviewed
• [Journal Article] Synergistic growth inhibition by 9-cis-retinoic acid plus trastuzumab in human hepatocellular carcinoma cells (2008)
  • Author(s): Tatebe H, et.al.
  • Journal Title: Clin Cancer Res 14 Pages: 2806-2812
  • Peer Reviewed
• [Journal Article] EGCG and Polyphenon E attenuate inflammation-related mouse colon carcinogenesis induced by AOM plus DDS (2008)
  • Author(s): Shirakami Y, et.al.
  • Journal Title: Mol Med Rep 1 Pages: 355-361
  • Peer Reviewed
• [Journal Article] (-)-Epigallocatechin gallate suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJ- db/db mice (2008)
  • Author(s): Shimizu M, et.al.
  • Journal Title: Cancer Prev Res 9 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Targeting Receptor Tyrosine kinases for chemoprevention by green tea catechin, EGCG (2008)
  • Author(s): Shimizu M, et.al.
  • Journal Title: Int J Mol Sci 9 Pages: 1034-1049
  • NAID: 120006341903
  • Peer Reviewed
• [Journal Article] Synergistic effects of PPARgamma ligands and retinoids in cancer treatment (2008)
  • Author(s): Shimizu M, Moriwaki H
  • Journal Title: PPAR Res 2008 Pages: 181047-181047
  • Peer Reviewed
• [Journal Article] Green tea extracts for the prevention of metachronous colorectal adenomas : a pilot study (2008)
  • Author(s): Shimizu M, et.al.
  • Journal Title: Cancer Epidemiol Biomarkers Prev 17 Pages: 3020-3025
  • Peer Reviewed
• [Journal Article] (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells (2008)
  • Author(s): Adachi S, et.al.
  • Journal Title: Carcinogenesis 29 Pages: 1986-1993
  • Peer Reviewed
• [Journal Article] EGCG inhiiibits activation of the insulin-like gorwth factor(ICF)/IGF-1 receptor axis in human hepatocellular carcinoma cells (2008)
  • Author(s): Shimizu M
  • Journal Title: Cancer Lett 262 Pages: 10-18
  • Peer Reviewed
• [Journal Article] EGCG and Polyphenon E eattenuate inflammation-related mouse colon carcinogenesis induced by AOM plus DDS (2008)
  • Author(s): Shirakami Y
  • Journal Title: Mol Med Res (In press)
  • Peer Reviewed
• [Journal Article] Synergistic Growth Inhibition by 9-cis-Retinoic Acid Plus Trastuzumab in Human Hepatocellular Carcinoma Cells (2008)
  • Author(s): Tatebe H
  • Journal Title: Clin Cancer Res (In press)
  • Peer Reviewed
• [Journal Article] Synergistic growth inhibition by acyclic retinoid and vitamin K2 in human hepatocellular carcinoma cells (2007)
  • Author(s): Kanamori T, Shimizu M, Okuno M, Matsushima-Nishiwaki R, Tsurumi H, Kojima S, Moriwaki H
  • Journal Title: Cancer Sci 98 Pages: 431-437
  • Peer Reviewed
• [Journal Article] Phosphorylated retinoid X receptor α loses its heterodimeric activity with retinoic acid receptor β (2007)
  • Author(s): Yoshimura K, Muto Y, Shimizu M, Matsushima-Nishiwaki R, Okuno M, Takano Y, Tsurumi H, Kojima S, Okano Y, Moriwaki H
  • Journal Title: Cancer Sci 98 Pages: 1868-1874
  • NAID: 10019996169
  • Peer Reviewed
• [Journal Article] Synergistic effects of RXRα and PPARγ ligands to inhibit growth in human colon cancer cells- phosphorylated RXRα is a critical target for colon cancer management- (2007)
  • Author(s): Yamazaki K, Shimizu M, Okuno M, Matsushima-Nishiwaki R, Kanemura N, Araki H, Tsurumi H, Kojima S, Weinstein IB, Moriwaki H
  • Journal Title: Gut 56 Pages: 1557-1563
  • Peer Reviewed
• [Journal Article] Phosphorylated retinoid X receptor alpha loses its heterodimeric activity with retinoic acid receptor beta. (2007)
  • Author(s): Yoshimura K
  • Journal Title: Cancer Sci 98 Pages: 1868-1874
  • Peer Reviewed
• [Journal Article] Synergistic effects of RXR alpha and PPAR gamma ligands to inhibit growth in human colon cancer cells-phosphorylated RXR alpha is a critical target for colon cancer management (2007)
  • Author(s): Yamazaki K
  • Journal Title: Gut 56 Pages: 1557-1563
  • Peer Reviewed
• [Journal Article] Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome (2006)
  • Author(s): Kojima Y, Tsurumi H, Goto N, Shimizu M, Kasahara S, Yamada T, Kanemura N, Hara T, Sawada M, Saio M, Yamada T, Takahashi T, Tomita E, Takami T, Moriwaki H
  • Journal Title: Eur J Haematol 76 Pages: 465-472
  • Peer Reviewed
• [Journal Article] Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma (2006)
  • Author(s): Goto N, Tsurumi H, Takemura M, Hara T, Sawada M, Kasahara S, Kanemura N, Yamada T, Shimizu M, Takahashi T, Tomita E, Seishima M, Takami T, Moriwaki H
  • Journal Title: Eur J Haematol 77 Pages: 217-225
  • Peer Reviewed
• [Journal Article] Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcome. (2006)
  • Author(s): Kojima Y
  • Journal Title: European Journal of Haematology 76 Pages: 465-472
• [Journal Article] Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma. (2006)
  • Author(s): Goto N
  • Journal Title: European Journal of Haematology 77 Pages: 217-225
• [Journal Article] Synergistic Growth Inhibition by Acyclic Retinoid and Vitamin K_2 in Human llepatocellular Carcinoma Cells.
  • Author(s): Kanamori T
  • Journal Title: Cancer Sci (in press)
• [Presentation] IGF/IGF-1Rを標的とした緑茶カテキンEGCGによる肥満関連大腸発癌の抑制 (2008)
  • Author(s): 清水雅仁、白上洋平、森脇久隆
  • Organizer: JDDW2008 ワークショップ18「機能性食品や薬物を用いた栄養代謝制御の試み」
  • Place of Presentation: 東京
  • Year and Date: 2008-10-04
• [Presentation] ワークショップ18「機能性食品や薬物を用いた栄養代謝制御の試み」IGF/IGF-1Rを標的とした緑茶カテキンEGCGによる肥満関連大腸発癌の抑制 (2008)
  • Author(s): 清水雅仁
  • Organizer: JDDW2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-04
• [Presentation] EGCG suppresses obesity-related colonic preneoplastic lesions in C57BL/KsJ-db/db mice (2008)
  • Author(s): Shimizu M, Shirakami Y, Hata K, Hirose Y, Tanaka T, Moriwaki H
  • Organizer: 99th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: サンディエゴ
  • Year and Date: 2008-04-14
• [Presentation] EGCG suppresses tumor growth by inhibiting activation of the VEGF/VEGFR axis in the xenograft model of human colon cancer and hepatoma. Shirakami Y (2008)
  • Author(s): Shirakami Y, Shimizu M, Sakai H, Tatebe H, Tanaka T, Moriwaki H
  • Organizer: 99th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: サンディエゴ
  • Year and Date: 2008-04-14
• [Presentation] (-)-Epigallocatechin Gallate Induces Phosphorylation of Epidermal growth factor Receptor via Activation of p38 MAPK in colon cancer cell (2008)
  • Author(s): Adachi S, To S, Shimizu M, Moriwaki H, Weinstein IB
  • Organizer: 99th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: サンディエゴ
  • Year and Date: 2008-04-14
• [Presentation] EGCG suppresses obesity-related colonic preneoplastic lesions in C57BL/KsJ-db/db mice (2008)
  • Author(s): Shimizu M
  • Organizer: 99^<th> AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2008-04-14
• [Presentation] EGCG suppresses tumor growth by inhibiting activation of the VEGF/VEGFR axis in the xenograft model of human colon cancer and hepatoma (2008)
  • Author(s): Shirakami Y
  • Organizer: 99^<th> AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2008-04-14
• [Presentation] (-)-Epigallocatechin Gallate Induces Phosphorylation of EpiTermal growth factor Receptor via Activation of p38 MAPK in colon cancer cells (2008)
  • Author(s): Adachi S
  • Organizer: 99^<th> AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: アメリカ・サンディエゴ
  • Year and Date: 2008-04-13
• [Presentation] Green Tea Catechins for the Prevention of Metachronous Colorectal Adenomas (2007)
  • Author(s): Shimizu M, Moriwaki H
  • Organizer: 第67回日本癌学会学術総会 ワークショップ22「Natural products & cancer chemoprevention」
  • Place of Presentation: 名古屋
  • Year and Date: 2007-10-30
• [Presentation] Effects of EGCG on activation of the IGF/ IGF-1R system in human colon and hepatoma cells (2007)
  • Author(s): Shimizu M, Shirakami Y, Moriwaki H
  • Organizer: Asian Pacific Digestive Week 2007 (APDW2007)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] Effects of EGCG on activation of the IGF/IGF-1R system in human hepatoma cell (2007)
  • Author(s): Shimizu M
  • Organizer: Asian Pacific Digestive Week 2007(APDW2007)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] Tumor-suppressing effects of green tea catechin on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y, Shimizu M, Tanaka T, Moriwaki H
  • Organizer: Asian Pacific Digestive Week 2007 (APDW2007)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-16
• [Presentation] Tumor-suppressing effects of green tea catechin on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y
  • Organizer: Asian Pacific Digestive Week 2007(APDW2007)
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-16
• [Presentation] 浜EGCG suppresses azoxymethane (AOM) -induced colonic premalignant lesions in male C57BL/KsJ-db/db (db/db) mice (2007)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Hata K, Hirose Y, Tanaka T, Moriwaki H
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Chemopreventive effects of green tea catechin on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y, Shimizu M, Tanaka T, Moriwaki H
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Effects of EGCG on activation of the IGF/ IGF-1R system in human hepatoma cells (2007)
  • Author(s): Sakai H, Shimizu M, Shirakami Y, Moriwaki H
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] EGCG suppresses azoxymethane(AOM)-induced colonic premalignant lesions in male C57BL/KsJ-db/db(db/db)mice (2007)
  • Author(s): Shimizu M
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Effects of EGCG on activation of the IGF/IGF-1R system in human hepatoma cell (2007)
  • Author(s): Sakai H
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Strategy and mechanism for the prevention of hepatocellular carcinoma (HCC) -Phosphorylated RXR・ might be a critical target for HCC chemoprevention- (2007)
  • Author(s): Shimizu M, Moriwaki H
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Chemopreventive effects of green tea catechin on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y, Shimizu M, Tanaka T, Moriwaki H
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Synergistic growth inhibition by 9-cis- retinoic acid plus trastuzumab in human hepatocellular carcinoma cells (2007)
  • Author(s): Tatebe H, Shimizu M, Shirakami Y, Sakai H, Moriwaki H
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Effects of EGCG on activation of the IGF/IGF-1R system in human hepatoma cells (2007)
  • Author(s): Sakai H, Shimizu M, Shirakami Y, Tatebe H, Moriwaki H
  • Organizer: The 8th Japan-Korean Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Strategy and mechanism for the prevention of hepatocellular carcinoma(HCC)-Phosphorylated RXRa might be a critical garget for HCC chemoprevention- (2007)
  • Author(s): Shimizu M
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium.
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Chemopreventive effects of green tea catechim on inflammation-related mouse colon carcinogenesis induced by AOM and DSS. (2007)
  • Author(s): Shirakami Y
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium.
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Synergistic growth inhibition by 9-cis-retinoic acid plus trastuzumab in human hepatocellular carcinoma cells. (2007)
  • Author(s): Tatebe H
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] Effects of EGCG on activation of the IGF/IGF-1R system in human hepatoma cell (2007)
  • Author(s): Sakai H
  • Organizer: The 8th Japan-Korea Cancer and Ageing Symposium
  • Place of Presentation: 岐阜
  • Year and Date: 2007-08-11
• [Presentation] EGCG suppresses azoxymethane- induced colonic premalignant lesions in male C57BL/KsJ-db/db mice (2007)
  • Author(s): Shimizu M, ShirakamiY, Sakai H, Hata H, Hirose Y, Tanaka T, Moriwaki H
  • Organizer: 98th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-17
• [Presentation] Chemopreventive effects of EGCG and polyphenon E on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y, Shimizu M, Tanaka T, Moriwaki H
  • Organizer: 98th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-17
• [Presentation] EGCG suppresses azoxymethane-induced colonic premalignant lesions in male C57BL/KsJ-db/db mice (2007)
  • Author(s): Shimizu M
  • Organizer: 98th AACR(American Association for Cancer Research)Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-17
• [Presentation] Chemopreventive effects of EGCG and polyphenon E on inflammation-related mouse colon carcinogenesis induced by AOM and DSS (2007)
  • Author(s): Shirakami Y
  • Organizer: 98th AACR (American Association for Cancer Research)Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-17
• [Presentation] Effects of EGCG on activation of the IGF/ IGF-1R system in human hepatoma cells (2007)
  • Author(s): Sakai H, Shimizu M, Shirakami Y, I. Bernard Weinstein, Moriwaki H
  • Organizer: 98th AACR (American Association for Cancer Research) Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-15
• [Presentation] Effects of EGCG on activation of the IGF/IGF-1R system in human hepatoma cell (2007)
  • Author(s): Sakai H
  • Organizer: 98th AACR(American Association for Cancer Research)Annual Meeting
  • Place of Presentation: ロサンゼルス
  • Year and Date: 2007-04-15
• [Book] Cancer : Disease Progression and Chemoprevention (2006)
  • Author(s): Shimizu M
  • Publisher: Research Signpost