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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #163506

Title: EPIGALLOCATECHIN-GALLATE (EGCG) INHIBITS VEGF-INDUCED ANGIOGENESIS BY SUPRESSING RECEPTOR COMPLEX FORMATION. PI3-KINASE ACTIVITY AND PRODUCTION OF IL-8 VIA NF- KAPPA-B PATHWAY

Author
item RODRIGUEZ, SHAUN - TUFTS-HNRCA
item LIU, LIPING - TUFTS-HNRCA
item BAND, MICHAEL - TUFTS-HNRCA
item MEYDANI, MOHSEN - TUFTS-HNRCA

Submitted to: Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2004
Publication Date: 3/24/2004
Citation: RODRIGUEZ, S., LIU, L., BAND, M., MEYDANI, M. EPIGALLOCATECHIN-GALLATE (EGCG) INHIBITS VEGF-INDUCED ANGIOGENESIS BY SUPRESSING RECEPTOR COMPLEX FORMATION. PI3-KINASE ACTIVITY AND PRODUCTION OF IL-8 VIA NF- KAPPA-B PATHWAY. EXPERIMENTAL BIOLOGY. 2004;18(4 PT I):A379-A380.

Interpretive Summary:

Technical Abstract: One of the mechanisms by which green tea may prevent cancer development is believed to be through its inhibition of angiogenesis. We have shown that the tea catechin EGCG inhibits tube formation of endothelial cells through the inhibition of Akt and VE-cadherin phosphorylation and by suppression of proangiogenic IL-8 production. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF-induced angiogenesis in vitro including formation of an essential receptor complex, activity of PI3-kinase, induction of IL-8, and activation of NF-kappaB, a transcription factor necessary for IL-8 production. Immunoprecipitation and Western blot analysis revealed that EGCG (0.5-20 micromole) dramatically inhibits the formation of the VEGFR2 receptor complex formed upon the binding of its ligand VEGF. EGCG also significantly decreases the activity of PI3-kinase in a dose-dependent manner. Gel shift assay revealed that EGCG also significantly decreased the activation and DNA-binding ability of NF-kappaB along with the suppression of IL-8 production at the mRNA (RT-PCR) and protein levels (ELISA). These results suggest that EGCG inhibits angiogenesis by suppressing a variety of VEGF-induced angiogenic processes and presents novel mechanisms by which a dietary component can modulate pathological processes.