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

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 mu mol/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 mu g/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 mu mol/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. (C) 2011 Elsevier Inc. All rights reserved.