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.
Shibata
Akira
A
Food & Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
Nakagawa
Kiyotaka
K
Sookwong
Phumon
P
Tsuduki
Tsuyoshi
T
Oikawa
Shinichi
S
Miyazawa
Teruo
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000098:blood supply; D042783:Endothelial Cells; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D014810:Vitamin E; C082097:tocotrienol, delta; D040262:Receptors, Vascular Endothelial Growth Factor; D020169:Caspases; D024502:alpha-Tocopherol