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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #175739


item Lai, Chao Qiang
item NIE, LIN
item Ordovas, Jose
item Meydani, Mohsen

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2007
Publication Date: 9/1/2008
Citation: Liu, L., Lai, C., Nie, L., Ordovas, J.M., Band, M., Moser, L., Meydani, M. 2008. THE MODULATION OF ENDOTHELIAL CELL GENE EXPRESSION BY GREEN TEA POLYPHENOL-EGCG. Molecular Nutrition and Food Research. 52:1182-1192.

Interpretive Summary: Epidemiological studies have shown that the consumption of green tea is associated with reduced risk of some cancers including stomach and esophagus cancer. Animal studies also suggest that green tea inhibits the development and progression of skin, lung, mammary gland, and gastrointestinal tract tumors. Green tea's protective effect has been attributed to the biological activities of a polyphenol catechin known as epigallocatechin gallate (EGCG), which has significant anti-proliferative and anti-cancer properties. Since this effect has not been fully clarified, we investigated the effect of EGCG as it affects gene expression in endothelial cells. Non-specific cell growth promoting genes were broadly suppressed by supplementation: two genes in particular inhibited growth, showing a growth suppression pattern. Further, several angiogenesis-related genes in endothelial cells were modified by EGCG supplementation and VEGF stimulation, indicating overall inhibition of angiogenesis, which is the formation of new blood vessels needed to feed tumor growth. Inflammation genes, which cause cell damage, were also modulated by EGCG in our experiments. Thus, we are beginning to understand the mechanism by which green tea EGCG may contribute to cancer prevention by reducing cell proliferation, tumor cell migration, and invasion and by inhibiting angiogenesis.

Technical Abstract: 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). 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 microarray. We found totally 80 genes were up-regulated and 58 genes were down-regulated by our interventions at p<0.005 level. The changes in expression of six genes were validated by real-time PCR. Our data show that EGCG down-regulated many cell proliferation related genes, which may be classified into three major groups: nonspecific transcription factors, cell cycle proteins, and translation initiative factors. Secondly, EGCG up-regulated two anti-proliferation genes: mitogen-responsive phosphoprotein and IGF binding protein-7 as well as an anti-angiogenesis gene, tryptophanyl-tRNA synthetase. Thirdly, EGCG down-regulated angiogenesis promoting genes, such as EGF response factor-2, interleukin (IL)-8, and ephrin-B2. Further, EGCG modulated inflammatory genes such as single Ig IL-1R-related molecule and regulated genes involved in glucose and cholesterol metabolism. Thus, we hypothesize that the anti-angiogenesis effect of EGCG was partially mediated through its broad inhibition of proliferation of endothelial cells as well as down-regulation of angiogenesis promoting genes and up-regulation of antiangiogenesis genes. Our data further support earlier observations of the anticancer effect of EGCG, which is modulated through changes in the expression of genes associated with angiogenesis and cell proliferation.