Antiangiogenic potency of vitamin E.
We investigated the antiangiogenic property and mechanism of vitamin E compounds, with particular emphasis on tocotrienol (T3), a natural analogue of tocopherol (Toc). T3 inhibited both the proliferation and tube formation of bovine aortic endothelial cells, with delta-T3 appearing to have the highest activity. delta-T3 also reduced the vascular endothelial growth factor (VEGF)-stimulated tube formation by human umbilical vein endothelial cells. Moreover, delta-T3 inhibited the new blood vessel formation on the growing chick embryo chorioallantoic membrane (assay for in vivo angiogenesis). Orally administered T3 suppressed the tumor cell-induced angiogenesis in the mouse dorsal air sac assay. In contrast with T3, Toc showed very weak inhibition. Based on DNA microarray analysis, antiangiogenic effect of T3 was attributable in part to regulation of intracellular VEGF signaling (phospholipase C-gamma and protein kinase C). Our findings suggest that T3 has potential as a therapeutic dietary supplement for preventing angiogenic disorders.
Miyazawa
Teruo
T
Food and Biodynamic Chemistry Lab, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan. miyazawa@biochem.tohoku.ac.jp
Tsuzuki
Tsuyoshi
T
Nakagawa
Kiyotaka
K
Igarashi
Miki
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002417:Cattle; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D024505:Tocopherols / Q000494:pharmacology; D024508:Tocotrienols / Q000494:pharmacology*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D024508:Tocotrienols; D042461:Vascular Endothelial Growth Factor A; D024505:Tocopherols