A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction
A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERβ signal transduction
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DOI：
10.1152/ajpendo.00187.2009
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发表时间：
2009-08-01
影响因子：
5.1
通讯作者：
Virgili, Fabio
中科院分区：
文献类型：
--
作者：
Comitato, Raffaella;Nesaretnam, Kalanithi;Virgili, Fabio
李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，李建军，等。天然维生素E对三烯醇活性的影响及其调控机制。[J] .中国生物医学工程学报，2009,31(4):557 - 557。2009年6月2日首次发表;doi: 10.1152 / ajpendo.00187.2009。维生素E是所有生育酚（TOC）和生育三烯醇（TT）衍生物的总称。在过去的几年里，有几篇论文表明，从棕榈油中提取的富含tt的部分（trf）可以抑制大量癌细胞的增殖并诱导细胞凋亡。然而，TT作用的分子机制尚不清楚。在本研究中，我们首次提出了一种涉及雌激素受体（ER）信号传导的TT活性新机制。计算机模拟和体外结合分析表明，TTs对ER α具有高亲和力，但对ER β没有亲和力。此外，在含有内质网β的MDA-MB-231乳腺癌细胞中，我们证明了tt增加内质网β转运到细胞核，这反过来激活雌激素反应基因（MIC-1， EGR-1和组织蛋白酶D），正如用内质网抑制剂ici - 182780进行细胞预培养所证明的那样。最后，我们观察到TT处理与细胞形态、DNA断裂和caspase-3激活的改变有关。总之，这些实验阐明了γ -和δ - tt效应的分子机制。
Comitato R, Nesaretnam K, Leoni G, Ambra R, Canali R, Bolli A, Marino M, Virgili F. A novel mechanism of natural vitamin E tocotrienol activity: involvement of ER beta signal transduction. Am J Physiol Endocrinol Metab 297: E427-E437, 2009. First published June 2, 2009; doi: 10.1152/ajpendo.00187.2009.-Vitamin E is a generic term used to indicate all tocopherol (TOC) and tocotrienol (TT) derivates. In the last few years, several papers have shown that a TT-rich fraction (TTRF) extracted from palm oil inhibits proliferation and induces apoptosis in a large number of cancer cells. However, the molecular mechanism(s) involved in TT action is still unclear. In the present study, we proposed for the first time a novel mechanism for TT activity that involves estrogen receptor (ER) signaling. In silico simulations and in vitro binding analyses indicated a high affinity of TTs for ER alpha but not for ER beta. In addition, in ER beta-containing MDA-MB-231 breast cancer cells, we demonstrated that TTs increase the ER beta translocation into the nucleus, which in turn activates estrogen-responsive genes (MIC-1, EGR-1 and cathepsin D), as demonstrated by cell preincubation with the ER inhibitor ICI-182,780. Finally, we observed that TT treatment is associated with alteration of cell morphology, DNA fragmentation, and caspase-3 activation. Altogether, these experiments elucidated the molecular mechanism underling gamma- and delta-TT effects.