...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nitric oxide-donating aspirin induces apoptosis in human colon cancer cells through induction of oxidative stress.
【24h】

Nitric oxide-donating aspirin induces apoptosis in human colon cancer cells through induction of oxidative stress.

机译：供一氧化氮的阿司匹林通过诱导氧化应激诱导人结肠癌细胞凋亡。

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

Nitric oxide-donating aspirin (NO-ASA) is a promising chemoprevention agent against colon cancer and other cancers. It consists of traditional ASA to which a NO-releasing moiety is bound through a spacer. NO-ASA inhibits colon cancer cell growth several hundred times more potently than does ASA. In Min mice, NO-ASA inhibited intestinal carcinogenesis without affecting cell proliferation. Thus, we examined whether NO-ASA's most important cell kinetic effect is the induction of apoptosis. After confirming induction of apoptosis in Min mice, we studied the underlying mechanism in human colon adenocarcinoma cells. NO-ASA's spacer formed a conjugate with glutathione, depleting glutathione stores. This induced oxidative stress (increased intracellular levels of peroxides and O(2)(.-)) leads to apoptosis by activating the intrinsic apoptosis pathway. NO-ASA disrupted adherens junctions by inducing cleavage of beta- and gamma-catenin, resulting in cell detachment. NO-ASA inhibited Wnt signaling by a dual mechanism: at low concentrations it blocked the formation of beta-catenin/Tcf complexes (dominant mechanism), and at higher concentrations it also cleaved beta-catenin. These findings provide a mechanism of action by a potent chemopreventive agent, underscore the significance of these pathways in regulating cell death in the context of cancer chemoprevention, and present a paradigm for developing agents with enhanced cancer cell growth inhibitory properties.
机译：捐赠一氧化氮的阿司匹林（NO-ASA）是一种有前途的化学预防剂，可预防结肠癌和其他癌症。它由传统的ASA组成，其中的NO释放部分通过一个间隔基与之结合。 NO-ASA对结肠癌细胞的抑制作用比ASA强数百倍。在Min小鼠中，NO-ASA抑制肠癌的发生而不影响细胞的增殖。因此，我们检查了NO-ASA是否最重要的细胞动力学作用是诱导细胞凋亡。在证实Min小鼠的凋亡诱导后，我们研究了人结肠腺癌细胞的潜在机制。 NO-ASA的间隔基与谷胱甘肽形成共轭物，耗尽了谷胱甘肽的储存量。这种诱导的氧化应激（增加的细胞内过氧化物和O（2）（.-）的细胞内水平）通过激活内在的细胞凋亡途径导致细胞凋亡。 NO-ASA通过诱导β-和γ-catenin的裂解，破坏粘​​附连接，导致细胞脱离。 NO-ASA通过双重机制抑制Wnt信号传导：在低浓度时，它会阻止β-catenin/ Tcf复合物的形成（主要机制），在高浓度时，它也会裂解β-catenin。这些发现提供了一种有效的化学预防剂的作用机制，强调了这些途径在癌症化学预防的背景下调节细胞死亡的重要性，并为开发具有增强的癌细胞生长抑制特性的药物提供了范例。

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