Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells.
The polyphenol epigallocatechin-3 gallate (EGCG) in green tea suppresses tumor growth by direct action on tumor cells and by inhibition of angiogenesis, but it is not known whether it specifically inhibits tumor angiogenesis. We examined the anti-angiogenic effect of EGCG on tumor-associated endothelial cells (TEC), endothelial progenitor cells (EPC), and normal endothelial cells (NEC). EGCG suppressed the migration of TEC and EPC but not NEC. EGCG also inhibited the phosphorylation of Akt in TEC but not in NEC. Furthermore, vascular endothelial growth factor-induced mobilization of EPC into circulation was inhibited by EGCG. MMP-9 in the bone marrow plasma plays key roles in EPC mobilization into circulation. We observed that expression of MMP-9 mRNA was downregulated by EGCG in mouse bone marrow stromal cells. In an in vivo model, EGCG suppressed growth of melanoma and reduced microvessel density. Our study showed that EGCG has selective anti-angiogenic effects on TEC and EPC. It is suggested that EGCG could be a promising angiogenesis inhibitor for cancer therapy.
Ohga
Noritaka
N
Department of Oral Pathology and Biology, Division of Oral Pathological Science, University of Hokkaido, Sapporo, Japan.
Hida
Kyoko
K
Hida
Yasuhiro
Y
Muraki
Chikara
C
Tsuchiya
Kunihiko
K
Matsuda
Kohei
K
Ohiro
Yoichi
Y
Totsuka
Yasunori
Y
Shindoh
Masanobu
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects*; D013662:Tea; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9