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gamma-Tocotrienol inhibits angiogenesis of human umbilical vein endothelial cell induced by cancer cell.


J Nutr Biochem  2011, 22 (12), 1127-36 DOI: 10.1016/j.jnutbio.2010.09.012
Li, Yang 1 ; Sun, Wen-Guang ; Liu, Hui-Kun ; Qi, Gui-Yun ; Wang, Qi ; Sun, Xiang-Rong ; Chen, Bing-Qing ; Liu, Jia-Ren

1.Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin 150081, People's Republic of China. liyang820119@sohu.com

Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of gamma-tocotrienol on tumor angiogenesis. The results showed that gamma-tocotrienol (10-40 mumol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. gamma-Tocotrienol (800-1200 mug/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of gamma-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 mumol/L gamma-tocotrienol. In addition, gamma-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of beta-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of gamma-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing beta-catenin expression. Thus, our results suggest that gamma-tocotrienol has a potential chemopreventive agent via antiangiogenesis.