...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >ET-18-OCH3 inhibits the phosphorylation and activation of p70 S6 kinase in MCF-7 cells.
【24h】

ET-18-OCH3 inhibits the phosphorylation and activation of p70 S6 kinase in MCF-7 cells.

机译：ET-18-OCH3抑制MCF-7细胞中p70 S6激酶的磷酸化和激活。

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

Alkyllysophospholipids (ALPs) inhibit the proliferation of epithelial cancer cells, and may achieve this by perturbing a number of intracellular signaling pathways. p70 S6 kinase (p70S6K) is a key intracellular signaling molecule in the regulation of cell proliferation. We therefore investigated whether ALPs inhibit p70S6K activity and, if so, whether this may be relevant in the mechanism of inhibition of cell proliferation by ALPs. In this study, we demonstrated that the prototypic ALP, 1-O-octadecyl-2-O-methyl-rac-glycerophosphocholine (ET-18-OCH3), inhibits the activation of p70S6K in MCF-7 cells but does not inhibit the activity of p70S6K. Inhibition of activation is achieved by preventing the phosphorylation of Thr389, Thr421, Ser424 and Ser411 residues of p70S6K, which are required for full activation of the kinase. ET-18-OCH3 inhibited insulin-stimulated activation of MCF-7 cells, which is sensitive to the phosphoinositide 3-kinase inhibitor LY294002, and to the m-Tor inhibitor rapamycin. Phorbol ester-induced activation of p70S6K which was sensitive to the m-Tor inhibitor but not the phosphoinositide 3-kinase inhibitor, was also inhibited by ET-18-OCH3. Hence the diminished phosphorylation of p70S6K by ET-18-OCH3 is a result of the inhibition of both phosphoinositide 3-kinase-dependent and -independent activation of p70S6K. The differential effects of ENE-OCH3, a phosphonocholine analog of ET-18-OCH3, on MCF-7 cell proliferation correlated with its effects on p70S6K activation. The data suggest that the inhibition of p70S6K activation of by ET-18-OCH3 contributes to the antiproliferative effects of ALPs in MCF-7 cells.
机译：烷基溶血磷脂（ALP）抑制上皮癌细胞的增殖，并可能通过干扰许多细胞内信号传导途径来实现。 p70 S6激酶（p70S6K）是细胞增殖调控中的关键细胞内信号分子。因此，我们研究了ALP是否抑制p70S6K活性，如果是，那么这可能与ALP抑制细胞增殖的机制有关。在这项研究中，我们证明了原型ALP 1-O-十八烷基-2-O-甲基-rac-甘油磷酸胆碱（ET-18-OCH3）抑制MCF-7细胞中p70S6K的激活，但不抑制其活性p70S6K。通过阻止p70S6K的Thr389，Thr421，Ser424和Ser411残基的磷酸化来实现激活抑制，这是激酶完全激活所必需的。 ET-18-OCH3抑制了胰岛素刺激的MCF-7细胞活化，该细胞对磷酸肌醇3激酶抑制剂LY294002和m-Tor抑制剂雷帕霉素敏感。 ET-18-OCH3也抑制了由间苯二酸酯引起的对m-Tor抑制剂敏感而不对磷酸肌醇3-激酶抑制剂激活的p70S6K活化。因此，ET-18-OCH3减少的p70S6K磷酸化是抑制p70S6K的磷酸肌醇3激酶依赖性和非依赖性活化的结果。 ENE-OCH3（ET-18-OCH3的磷酸胆碱类似物）对MCF-7细胞增殖的差异作用与其对p70S6K活化的作用相关。数据表明，ET-18-OCH3对p70S6K激活的抑制作用有助于ALP在MCF-7细胞中的抗增殖作用。

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