The modulation of endothelial cell gene expression by green tea polyphenol-EGCG.
Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (-)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation.
Liu
Liping
L
Vascular Biology Laboratory, JM USDA Human Nutrition Center on Aging at Tufts University, Boston, MA 02111, USA.
Lai
Chao-Qiang
CQ
Nie
Lin
L
Ordovas
Jose
J
Band
Michael
M
Moser
Leta
L
Meydani
Mohsen
M
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D042442:Vascular Endothelial Growth Factors; D002392:Catechin; C045651:epigallocatechin gallate