• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Nutritional Biochemistry >Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells.
【24h】

Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells.

机译：γ-生育三烯酚诱导的凋亡与人乳腺癌细胞中未折叠的蛋白反应有关。

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Gamma-tocotrienol ( gamma-T3) is a member of the vitamin E family. Tocotrienols (T3s) are powerful antioxidants and possess anticancer, neuroprotective and cholesterol-lowering properties. Tocotrienols inhibit the growth of various cancer cell lines without affecting normal cells. Less is known about the exact mechanisms of action of T3s on cell death and other growth inhibitory pathways. In the present study, we demonstrate that gamma-T3 induces apoptosis in MDA-MB 231 and MCF-7 breast cancer cells as evident by PARP cleavage and caspase-7 activation. Gene expression analysis of MCF-7 cells treated with gamma-T3 revealed alterations in the expression of multiple genes involved in cell growth and proliferation, cell death, cell cycle, cellular development, cellular movement and gene expression. Further analysis of differentially modulated genes using Ingenuity Pathway Analysis software suggested modulation of canonical signal transduction or metabolic pathways such as NRF-2-mediated oxidative stress response, TGF- beta signaling and endoplasmic reticulum (ER) stress response. Analysis of ER-stress-related proteins in MCF-7 and MDA-MB 231 cells treated with gamma-T3 demonstrated activation of PERK and pIRE1 alpha pathway to induce ER stress. Activating transcription factor 3 (ATF3) was identified as the most up-regulated gene (16.8-fold) in response to gamma-T3. Activating transcription factor 3 knockdown using siRNA suggested an essential role of ATF3 in gamma-T3-induced apoptosis. In summary, we demonstrate that gamma-T3 modulates ER stress signaling and have identified ATF3 as a molecular target for gamma-T3 in breast cancer cells
机译：γ-生育三烯酚（γ-T3）是维生素E家族的成员。生育三烯酚（T3）是强大的抗氧化剂，并具有抗癌，神经保护和降低胆固醇的特性。生育三烯酚可抑制各种癌细胞系的生长，而不会影响正常细胞。关于T3对细胞死亡和其他生长抑制途径的确切作用机理知之甚少。在本研究中，我们证明了PPAR裂解和caspase-7激活可证明，γ-T3诱导MDA-MB 231和MCF-7乳腺癌细胞凋亡。用γ-T3处理的MCF-7细胞的基因表达分析揭示了参与细胞生长和增殖，细胞死亡，细胞周期，细胞发育，细胞运动和基因表达的多个基因表达的变化。使用Ingenuity Pathway Analysis软件对差异调节基因进行的进一步分析表明，对规范信号转导或代谢途径（例如NRF-2介导的氧化应激反应，TGF-β信号传导和内质网（ER）应激反应）的调节。 γ-T3处理的MCF-7和MDA-MB 231细胞中与ER应激有关的蛋白质的分析表明，PERK和pIRE1 alpha途径活化可诱导ER应激。激活转录因子3（ATF3）被确定为响应γ-T3的最上调基因（16.8倍）。使用siRNA激活转录因子3敲低提示ATF3在γ-T3诱导的细胞凋亡中具有重要作用。总之，我们证明了γ-T3调节内质网应激信号并已确定ATF3为乳腺癌细胞中γ-T3的分子靶标

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号