The α-tocopherol derivative ESeroS-GS induces cell death and inhibits cell motility of breast cancer cells through the regulation of energy metabolism
The α-tocopherol derivative ESeroS-GS induces cell death and inhibits cell motility of breast cancer cells through the regulation of energy metabolism
复制标题
α-生育酚衍生物ESeroS-GS通过调节能量代谢诱导细胞死亡并抑制乳腺癌细胞的细胞运动。
DOI：
10.1016/j.ejphar.2014.09.050
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发表时间：
2014-12-15
影响因子：
5
通讯作者：
Wei, Taotao
中科院分区：
文献类型：
--
作者：
Zhao, Lijing;Zhao, Xingyu;Wei, Taotao
已知癌细胞与正常细胞相比表现出不同的特征。因此，靶向这些特征可以改善对癌症治疗的反应。在这项研究中，我们提供了直接的证据表明，α-Locopherol衍生物ESeroS-GS抑制乳腺癌细胞的活力，迁移和侵袭。ESeroS-GS以剂量依赖性方式诱导不同癌细胞中的细胞死亡，但对MCF-10A乳腺上皮细胞无显著影响。虽然ESeroS-GS诱导的MDA-MB-231乳腺癌细胞死亡伴随着活性氧的产生和线粒体膜电位（MMP）的下调，但在MCF-10A细胞中未观察到这种对活性氧和MMP的影响。进一步的研究表明，ESeroS-GS下调了己糖激酶II、SDH B的表达。UQCRC 2和考克斯II在MDA-MB-231细胞中表达，但在MCF-10A细胞中不表达。这些酶的下调解释了ESeroS-GS处理后MDA-MB-231细胞中氧化磷酸化（OXPHOS）和糖酵解的减少。亚毒性浓度或ESeroS-GS处理后，MDA-MB-231细胞的F-actin骨架组装受损，细胞的迁移和侵袭能力下降，这可能与细胞能量代谢受到抑制有关。这些结果表明，ESeroS-GS显示出通过靶向癌细胞的能量代谢而成为新型抗癌剂的潜力。(C)2014爱思唯尔有限公司版权所有。
Cancer cells are known to exhibit different hallmarks compared with normal cells. Therefore, targeting these features may improve the response to cancer therapy. In this study, we provided direct evidence that the alpha-Locopherol derivative ESeroS-GS inhibited the viability, migration, and invasion of breast cancer cells. ESeroS-GS induced cell death in different cancer cells in a dose dependent manner but showed no significant effects on MCF-10A mammary epithelial cells. Although the ESeroS-GS-induced cell death in MDA-MB-231 breast cancer cells was accompanied with the generation of reactive oxygen species and the down regulation of mitochondrial membrane potential (MMP), no such effect on reactive oxygen species and MMP was seen in MCF-10A cells. Further studies indicated that ESeroS-GS down regulated the expression of hexokinase II, SDH B. UQCRC2 and COX II in MDA-MB-231 cells but not in MCF-10A cells. The down-regulation of these enzymes accounts for the decreased oxidative phosphorylation (OXPHOS) and glycolysis in MDA-MB-231cells upon ESeroS-GS treatment. We also found that sub-toxic concentration or ESeroS-GS treatment resulted in the impairment of F-actin cytoskeleton assembly and the consequently decreased migratory and invasive ability of MDA-MB-231 cells, which might be due to the inhibition of cellular energy metabolism. These results indicate that ESeroS-GS shows potential to become a novel anti-cancer agent by targeting the energy metabolism of cancer cells. (C) 2014 Elsevier B.V. All rights reserved.