2009 Fiscal Year Final Research Report
Targeting of the preventive effect of EGCG ((-)-epigallocatechin-3-gallate) on lipid rafts in colon cancer cells
Project/Area Number |
20790490
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Single-year Grants |
Research Field |
Gastroenterology
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Research Institution | Gifu University |
Principal Investigator |
SEIJI Adachi Gifu University, 大学院・医学系研究科, 助教 (50467205)
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Project Period (FY) |
2008 – 2009
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Keywords | EGCG / EGFR / p38MAPキナーゼ / 脂質ラフト / 内在化 |
Research Abstract |
We previously reported that (-)-epigallocatechin gallate (EGCG) in green tea alters plasma membrane organization and causes internalization of epidermal growth factor receptor (EGFR), resulting in the suppression of colon cancer cell growth. In the present study, we investigated the detailed mechanism underlying EGCG-induced downregulation of EGFR in SW480 colon cancer cells. Prolonged exposure to EGCG caused EGFR degradation, concurrently inducing phosphorylation of p38 mitogen-activated protein kinase (MAPK). The inhibition of p38 MAPK by SB203580, a specific p38 MAPK inhibitor, or p38 MAPK-siRNA suppressed the internalization and subsequent degradation of EGFR induced by EGCG. Moreover, EGCG caused phosphorylation of EGFR at Ser1046/1047, a site which is critical for its downregulation and this was also suppressed by SB203580 or siRNA of p38 MAPK. Taken together, our results strongly suggest that phosphorylation of EGFR at serine 1046/1047 via activation of p38 MAPK plays a pivotal role in EGCG-induced downregulation of EGFR in colon cancer cells.
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[Journal Article] Rho-kinase limits FGF-2-stimulated VEGF release in osteoblasts.2010
Author(s)
Natsume H, Tokuda H, Adachi S, Takai S, Matsushima-Nishiwaki R, Kato K, Minamitani C, Niida S, Mizutani J, Kozawa O, Otsuka T
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Journal Title
Peer Reviewed
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[Journal Article] The involvement of thromboxane A2 in the elevation of soluble CD40 ligand levels in atherosclerotic patients2010
Author(s)
Enomoto Y, Adachi S, Matsushima-Nishiwaki R, Doi T, Niwa M, Akamatsu S, Tokuda H, Yoshimura S, Ogura S, Iwama T, Kozawa O
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Journal Title
Atherosclerosis 209
Pages: 414-421
Peer Reviewed
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[Journal Article] Antithrombin III suppresses ADP-induced platelet granule secretion: Inhibition of HSP27 phosphorylation.2009
Author(s)
Doi T, Adachi S, Takai S, Matsushima-Nishiwaki R, Kato H, Enomoto Y, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Iwama T, Kozawa O, Ogura S
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Journal Title
Arch Biochem Biophys 489
Pages: 62-7
Peer Reviewed
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[Journal Article] αB-crystallin suppresses ADP-induced granule secretion from human platelets.2009
Author(s)
Enomoto Y, Adachi S, Matsushima-Nishiwaki R, Niwa M, Tokuda H, Akamatsu S, Doi T, Kato H, Yoshimura S, Ogura S, Iwama T, Kozawa O
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Journal Title
FEBS Lett 583
Pages: 2464-8
Peer Reviewed
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[Journal Article] (-)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt pathway in osteoblasts.2009
Author(s)
Natsume H, Adachi S, Takai S, Tokuda H, Matsushima-Nishiwaki R, Yamauchi J, Kato H, Kato K, Mizutani J, Otsuka T, Kozawa O
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Journal Title
Int J Mol Med 24
Pages: 197-203
Peer Reviewed
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[Journal Article] Tacrolimus but not cyclosporine A enhances FGF-2-induced VEGF release in osteoblasts.2009
Author(s)
Yamauchi J, Takai S, Matsushima-Nishiwaki R, Adachi S, Minamitani C, Natsume H, Mizutani J, Otsuka T, Takeda J, Harada A, Kozawa O, Tokuda H
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Journal Title
Int J Mol Med 23
Pages: 267-72
Peer Reviewed
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[Journal Article] Phosphorylated heat shock protein 27 represses growth of hepatocellular carcinoma via inhibition of extracellular-signal-regulated kinase.2008
Author(s)
Matsushima-Nishiwaki R, Takai S, Adachi S, Minamitani C, Yasuda E, Noda T, Kato K, Toyoda H, Kaneoka Y, Yamaguchi A, Kumada T, Kozawa O
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Journal Title
J Biol Chem 283
Pages: 18852-60
Peer Reviewed
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[Journal Article] HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion.2008
Author(s)
Kato H, Takai S, Matsushima-Nishiwaki R, Adachi S, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Doi T, Ogura S, Kozawa O
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Journal Title
Arch Biochem Biophys 475
Pages: 80-6
Peer Reviewed
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