• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Therapeutic potential of sulindac hydroxamic acid against human pancreatic and colonic cancer cells.
【24h】

Therapeutic potential of sulindac hydroxamic acid against human pancreatic and colonic cancer cells.

机译：舒林酸异羟肟酸对人胰腺癌和结肠癌细胞的治疗潜力。

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

The non-steroidal anti-inflammatory drug (NSAID) sulindac exhibits cyclooxygenase (COX)-dependent and COX-independent chemopreventive properties in human cancer. The present study was aimed at investigating whether the hydroxamic acid substitution for the carboxylic acid group could enhance the in vitro antitumor and antiangiogenic activities of sulindac. Characterization tools used on this study included analyses of cell viability, caspase 3/7 induction, DNA fragmentation, and gene expression. Our findings demonstrate that the newly synthesized hydroxamic acid derivative of sulindac and its sulfone and sulfide metabolites were characterized by a good anticancer activity on human pancreatic and colon cancer cells, both in terms of potency (IC(50) mean values from 6 +/- 1.1 muM to 64 +/- 1.1 muM) and efficacy (E(max) of approximately 100%). Hydroxamic acid derivatives trigger a higher degree of apoptosis than carboxylic acid counterparts, increase bax/bcl-2 expression ratio and induce caspase 3/7 activation. Most notably, these compounds significantly inhibit proangiogenic growth factor-stimulated proliferation of vascular endothelial cell (HUVEC) at sub-micromolar concentrations. Our data also provide evidence that the COX-active metabolite of sulindac hydroxamic acid were the most active of the series and selective inhibition of COX-1 but not COX-2 can mimic its effects, suggesting that COX inhibition could only play a partial role in the mechanism of compound action. In conclusion, these data demonstrate that substitution of the carboxylic acid group with the hydroxamic acid moiety enhances in vitro antiproliferative, proapoptotic and antiangiogenic properties of sulindac, therefore increasing the therapeutic potential of this drug.
机译：非甾体类抗炎药（NSAID）舒林酸在人类癌症中表现出环加氧酶（COX）依赖性和COX依赖性化学预防特性。本研究旨在研究异羟肟酸取代羧酸基团是否可以增强舒林酸的体外抗肿瘤和抗血管生成活性。这项研究中使用的表征工具包括细胞活力分析，胱天蛋白酶3/7诱导，DNA片段化和基因表达。我们的发现表明，新合成的舒林酸异羟肟酸衍生物及其砜和硫化物代谢物的功效对人胰腺癌和结肠癌细胞具有良好的抗癌活性，其效价均从6 +/-（IC（50）平均值1.1μM至64 +/- 1.1μM）和功效（E（max）约为100％）。异羟肟酸衍生物比羧酸对应物触发更高程度的凋亡，增加bax / bcl-2表达比并诱导caspase 3/7活化。最值得注意的是，这些化合物在亚微摩尔浓度下可显着抑制促血管生成生长因子刺激的血管内皮细胞（HUVEC）增殖。我们的数据还提供了证据，舒林酸异羟肟酸的COX活性代谢产物是该系列中最活跃的，选择性抑制COX-1而不是COX-2可以模拟其作用，这表明COX抑制只能在以下方面发挥部分作用：复合作用的机制。总之，这些数据表明用异羟肟酸部分取代羧酸基团可增强舒林酸的体外抗增殖，促凋亡和抗血管生成特性，因此增加了该药物的治疗潜力。

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