α-Tocopherol suppresses antiangiogenic effect of δ-tocotrienol in human umbilical vein endothelial cells

Recently, tocotrienol (T3), a less well-known form of vitamin E, has gained attention as a potent hypocholesterolemic, anticancer and antiangiogenic agent. However, tocopherol (Toc), a commonly consumed form of vitamin E, has been reported to inhibit T3's effects (hypocholesterolemic and anticancer activity). There has been no report on Toc's effect on the antiangiogenic action of T3 during cotreatment The aim of this study is to determine if and to what extent Toc affects the antiangiogenic effects of delta-T3 (the most potent isomer). This was achieved through cotreatment of human umbilical vein endothelial cells (HUVECs) with delta-T3 and Toc (alpha-,beta-,gamma- and delta-isomers). Toc, especially a-Toc, attenuated delta-T3-induced cytotoxicity and tube degradation in cotreated HUVECs, while a-Toc treatments did not exhibit any effects. A rat aortic ring assay also showed inhibition of delta-T3's antiangiogenic effects by a-Toc. Further, in HUVEC study, cell cycle arrest and proapoptotic gene expression (p21, p27, caspase-3 and caspase-9) which were induced by delta-T3 were decreased by ot-Toc treatment. a-Toc also suppressed delta-T3-induced dephosphorylation of vascular endothelial growth factor receptor 2 and Akt pathway proteins. Additionally, uptake of delta-T3 into HUVECs was decreased by a-Toc. Here we demonstrate that a-Toc not only has little antiangiogenic effect on endothelial cells but also reduces the antiangiogenic effects of delta-T3 through modulation of its cellular uptake and of relevant signal transduction pathways. Understanding T3's antiangiogenic effects and interaction with Toc is important for developing medical applications. (C) 2015 Elsevier Inc. All rights reserved.