...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells
【24h】

Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells

机译：突变的p53 Notch1信号轴参与姜黄素诱导的乳腺癌细胞凋亡。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.
机译：据报道，Notch1在三阴性和其他亚型乳腺癌中高表达。突变p53（R280K）在MDA-MB-231三阴性人类乳腺癌细胞中过表达。本研究旨在确定突变体p53是否可以是MDA-MB-231细胞中Notch1的有效转录激活因子，并探讨该突变体p53-Notch1轴在姜黄素诱导的细胞凋亡中的作用。我们发现姜黄素治疗可诱导MDA-MB-231细胞凋亡，并下调Notch1及其下游靶标Hes1。确定Notch1表达的这种降低是由于内源性突变体p53活性降低所致。我们通过执行Notch1启动子驱动的报告基因分析证实姜黄素对Notch1转录的抑制作用，并通过EMSA和染色质免疫沉淀分析在Notch1启动子中鉴定出一个假定的p53结合位点。突变体p53的过表达增加了Notch1启动子的活性，而通过小的干扰RNA抑制突变体p53的表达抑制了Notch1的表达，从而诱导了细胞凋亡。此外，姜黄素诱导的凋亡通过Notch1或突变体p53的敲低而进一步增强，但由于活性Notch1的过表达而降低。两者合计，我们的结果首次证明，Notch1是乳腺癌细胞中突变体p53的转录靶标，并表明靶向突变体p53和/或Notch1可以与化学疗法相结合，以改善乳腺癌的反应癌细胞为姜黄素。

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