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首页> 外文期刊>American Journal of Physiology >A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction.
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A novel mechanism of natural vitamin E tocotrienol activity: involvement of ERbeta signal transduction.

机译：天然维生素E生育三烯酚活性的新机制：ERbeta信号转导。

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摘要

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 ERbeta but not for ERalpha. In addition, in ERbeta-containing MDA-MB-231 breast cancer cells, we demonstrated that TTs increase the ERbeta 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.
机译：维生素E是用于表示所有生育酚（TOC）和生育三烯酚（TT）衍生物的通用术语。在最近几年中，几篇论文表明，从棕榈油中提取的富含TT的馏分（TTRF）抑制增殖并诱导大量癌细胞的凋亡。然而，参与TT作用的分子机制仍不清楚。在本研究中，我们首次提出了涉及雌激素受体（ER）信号传导的TT活性新机制。在计算机模拟和体外结合分析中，TT对ERbeta的亲和力很高，但对ERalpha却没有。此外，在含有ERbeta的MDA-MB-231乳腺癌细胞中，我们证明了TT会增加ERbeta易位进入细胞核，进而激活雌激素反应性基因（MIC-1，EGR-1和组织蛋白酶D），与ER抑制剂ICI-182,780一起进行细胞预孵育证明。最后，我们观察到TT治疗与细胞形态改变，DNA片段化和caspase-3激活有关。总之，这些实验阐明了γ-和δ-TT作用的分子机制。

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