Miyazawa Teruo, Tsuzuki Tsuyoshi, Nakagawa Kiyotaka, Igarashi Miki
Food and Biodynamic Chemistry Lab, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
Ann N Y Acad Sci. 2004 Dec;1031:401-4. doi: 10.1196/annals.1331.057.
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.
我们研究了维生素E化合物的抗血管生成特性及机制，尤其着重于生育三烯酚（T3），它是生育酚（Toc）的一种天然类似物。T3抑制牛主动脉内皮细胞的增殖和管腔形成，其中δ-T3似乎具有最高活性。δ-T3还减少了血管内皮生长因子（VEGF）刺激的人脐静脉内皮细胞的管腔形成。此外，δ-T3抑制了发育中的鸡胚绒毛尿囊膜上的新血管形成（体内血管生成测定）。口服T3在小鼠背气囊试验中抑制肿瘤细胞诱导的血管生成。与T3相比，Toc显示出非常微弱的抑制作用。基于DNA微阵列分析，T3的抗血管生成作用部分归因于细胞内VEGF信号传导（磷脂酶C-γ和蛋白激酶C）的调节。我们的研究结果表明，T3作为预防血管生成紊乱的治疗性膳食补充剂具有潜力。
