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维生素 E 衍生物通过调节 MCF7 细胞的细胞脂质和膜动力学诱导细胞凋亡。

Vitamin E Derivative with Modified Side Chain Induced Apoptosis by Modulating the Cellular Lipids and Membrane Dynamics in MCF7 Cells.

机构信息

The Scientific and Technological Research Council of Turkey, Ankara, Turkey.

Department of Vitamins and Coenzymes Biochemistry, Palladin Institute of Biochemistry, Kiev, Ukraine.

出版信息

Cell Biochem Biophys. 2021 Jun;79(2):271-287. doi: 10.1007/s12013-020-00961-y. Epub 2021 Jan 13.

Abstract

The vitamin E derivative with side chain modification (TC6OAc) has been shown to possess anticancer activity in our earlier in vivo studies. It was hypothesized that, as Vitamin E (VE) and VE derivative are fat soluble lipophilic molecules, they exert their function by modulating the lipid metabolism and related pathways. This study aimed to evaluate the cellular impact of this VE derivative (2,5,7,8-Tetramethyl-2-(4'-Methyl-3'-Pentenyl)-6-Acetoxy Chromane-TC6OH), using α-tocopherol as a reference compound throughout the experiments. Their effects on the cellular metabolism, the biophysical properties of cellular lipids and the functional characteristics of cells were monitored in human estrogen receptor (ER) positive breast cancer cells. It has been documented that TC6OH treatment induces tumor cell apoptosis by dissipating the mitochondrial membrane potential, modulating the lipid, transportation and degradation as well as downregulating certain anti-apoptotic and growth factor related proteins. Due to resistance of ER positive cells to the established therapies, the findings of this study are of translational value.

摘要

侧链修饰的维生素 E 衍生物(TC6OAc)在我们早期的体内研究中显示出具有抗癌活性。据推测,由于维生素 E(VE)和 VE 衍生物是脂溶性亲脂性分子,它们通过调节脂质代谢和相关途径发挥作用。本研究旨在使用 α-生育酚作为参考化合物,评估这种 VE 衍生物(2,5,7,8-四甲基-2-(4'-甲基-3'-戊烯基)-6-乙酰氧基色满-TC6OH)对细胞的影响。在人雌激素受体(ER)阳性乳腺癌细胞中监测其对细胞代谢、细胞脂质的生物物理特性以及细胞功能特性的影响。有文献记载,TC6OH 通过耗散线粒体膜电位、调节脂质转运和降解以及下调某些抗凋亡和生长因子相关蛋白来诱导肿瘤细胞凋亡。由于 ER 阳性细胞对现有治疗方法的耐药性,本研究的发现具有转化价值。

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