Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate.
OBJECTIVE
Green tea consumption has been linked to a reduced occurrence of some tumor types. Current data indicate that the principal mediator of this chemopreventive effect is epigallocatechin-3-gallate (EGCG), the most abundant polyphenol found in dried tea leaves. Here, we examined the effects of this compound on the two key cell populations typically involved in tumor growth: tumor cells and endothelial cells.


METHODS
The effects of green tea and EGCG were tested in a highly vascular Kaposi's sarcoma (KS) tumor model and on endothelial cells in a panel of in vivo and in vitro assays.


RESULTS
EGCG inhibited KS-IMM cell growth and endothelial cell growth, chemotaxis, and invasion over a range of doses; high concentrations also induced tumor cell apoptosis. EGCG inhibited the metalloprotease-mediated gelatinolytic activity produced by endothelial cell supernatants and the formation of new capillary-like structures in vitro. Green tea or purified EGCG when administered to mice in the drinking water inhibited angiogenesis in vivo in the Matrigel sponge model and restrained KS tumor growth. Histological analysis of the tumors were consistent with an anti-angiogenic activity of EGCG and green tea.


CONCLUSIONS
These data suggest that the green tea gallate or its derivatives may find use in the prevention and treatment of vascular tumors in a chemoprevention or adjuvant setting.
Tumor Progression Unit and Molecular Oncology Lab, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Gianfranco
G
Fassina
Roberta
R
Venè
Monica
M
Morini
Simona
S
Minghelli
Roberto
R
Benelli
Douglas M
DM
Noonan
Adriana
A
Albini
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D028321:Plant Preparations / Q000494:pharmacology; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000517:prevention & control; D013662:Tea; D019043:Vascular Neoplasms / Q000473:pathology / Q000517:prevention & control*; D023041:Xenograft Model Antitumor Assays
D028321:Plant Preparations; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9