delta-Tocotrienol suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not.

Recently, tocotrienol (T3), a less well-known form of vitamin E, has gained considerable attention as a potent antiangiogenic agent. However, the majority of vitamin E research has focused on tocopherol (Toc), with some studies indicating alpha-Toc may prevent tumor angiogenesis. In this study, we aimed to clarify the differences in antiangiogenic potential between delta-T3 and alpha-Toc. We showed delta-T3 (2.5-5 microM) completely abolished proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), whereas a similar dose of alpha-Toc had no such effects. delta-T3 suppressed VEGF receptor 2 (VEGFR-2) signaling, and activated caspases in HUVECs. In addition, via an in vivo mouse Matrigel plug angiogenesis assay, we found that delta-T3 (30 microg), but not alpha-Toc, inhibited tumor cell-induced vessel formation. In summary, our results demonstrate delta-T3 has superior antiangiogenic activities to alpha-Toc, and provide insights into the different mechanisms responsible for this effect of T3 and Toc.