Author
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MEYDANI, MOHSEN - TUFTS/HNRCA |
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Submitted to: Journal of Nutrition
Publication Type: Abstract Only Publication Acceptance Date: 6/7/2004 Publication Date: 12/1/2004 Citation: Meydani, M., 2004. Molecular mechanism of egcg inhibition of angiogenesis. [abstract]. Journal of Nutrition. 134(12S0:3519S. Interpretive Summary: Technical Abstract: Green tea may prevent cancer development via several mechanisms. One of the mechanisms is believed to be through its inhibition of tumor angiogenesis. Earlier, we have shown that the green tea catechins including epigallocatechin gallate (EGCG) inhibit angiogenesis through the inhibition of Akt and VE-cadherin phosphorylation and by suppression of the production of the pro-angiogenic cytokine, IL-8. To further elucidate the anti-angiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF-induced angiogenesis in vitro including the formation of an essential receptor complex, activity of PI3-kinase, induction of IL-8, and activation of nuclear factor, a transcription factor necessary for IL-8 production. Immunoprecipitation and Western blot analysis revealed that EGCG (0.5-20 microM) significantly inhibits the formation of the VEGFR2, VE-cadherin, beta-catenin, and PI3-kinase complex formation upon the binding of its ligand VEGF. EGCG also significantly decreases the activity of PI3-kinase in a dose-dependent manner. Gel shift assay showed 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 and protein levels. Our results suggest that EGCG inhibition of angiogenesis is mediated through suppression of a variety of VEGF-induced angiogenic processes and presents novel mechanisms by which a dietary component can modulate pathological processes. |
