...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >The strigolactone analog GR-24 inhibits angiogenesis in vivo and in vitro by a mechanism involving cytoskeletal reorganization and VEGFR2 signalling
【24h】

The strigolactone analog GR-24 inhibits angiogenesis in vivo and in vitro by a mechanism involving cytoskeletal reorganization and VEGFR2 signalling

机译：杂芳酮类似物GR-24通过涉及细胞骨骼重组和VEGFR2信号传导的机制抑制体内和体外体内的血管生成

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

Phytohormones have shown great potential as natural anticancer compounds, being interesting in cancer prevention and therapy. Strigolactones are a class of plant hormones involved in the inhibition of root branching and sprouting. The antiproliferative capacity of the synthetic strigolactone analog GR-24 has been described against breast cancer cell lines in vitro. In this study, we show for the first time that GR-24 is a potent antiangiogenic compound in vivo and in vitro. In the in vivo tests, GR-24 shows a great inhibitory effect on vasculature formation in the chicken chorioallantoic membrane and in two different zebrafish models. Our in vitro results show that GR-24 inhibits the growth of endothelial cells and different cancer cell lines with a micromolar range of half inhibitory concentration (IC50) values. In addition, GR-24 inhibits key steps of the angiogenic process in vitro, such as tubulogenesis, invasion, extracellular matrix remodeling capacity, migration and adhesion of endothelial cells at non-cytotoxic concentrations. Our data point to an effect of GR-24 on cytoskeleton organization in endothelial cells, in addition to a decrease in focal adhesion kinase (FAK) presence in these cells. All these data, together with the observed increase in surface expression of vascular endothelial-cadherin (VE-cadherin) and platelet and endothelial cell adhesion molecule 1 (PECAM-1), suggest that GR-24 prevents angiogenesis by maintaining the quiescent phenotype in endothelial cells. The proposed mechanism of action underlying the antiangiogenic activity of GR-24 involves the inhibition of VEGFR2 phosphorylation, and the downstream reduction in activation of FAK, a key regulator protein implicated in angiogenesis. Our results suggest that GR-24 may be a promising new compound for antiangiogenic therapy of cancer and other angiogenesis-dependent diseases.
机译：植物肠酮表现出巨大的潜力作为天然抗癌化合物，是有趣的癌症预防和治疗。杂草酮是一类植物激素，参与了根部分支和发芽的抑制作用。已经在体外对乳腺癌细胞系描述了合成杂酮模拟GR-24的抗增殖能力。在这项研究中，我们首次展示GR-24是体内和体外有效的抗血管生成化合物。在体内试验中，GR-24显示了鸡绒铃炎膜和两种不同斑马皮模型的血管系统形成的极大抑制作用。我们的体外结果表明，GR-24抑制内皮细胞的生长和不同的癌细胞系具有微摩尔的半抑制浓度（IC 50）值。此外，GR-24在非细胞毒性浓度下抑制体外血管生成过程的关键步骤，例如小管发生，侵袭，内皮细胞的侵袭，内皮细胞的粘附性。除了这些细胞中局灶性粘附激酶（FAK）存在的降低之外，我们的数据指向GR-24对内皮细胞中的细胞骨架组织的影响。所有这些数据以及观察到的血管内皮 - 钙粘蛋白（Ve-Cadherin）和血小板和内皮细胞粘附分子1（PECAM-1）的表面表达的增加，表明GR-24通过在内皮中维持静态表型来防止血管生成细胞。 GR-24的抗血管生成活性下面的提出的作用机制涉及VEGFR2磷酸化的抑制，以及FAK活化的下游减少，该关键调节剂蛋白质涉及血管生成。我们的研究结果表明，GR-24可能是癌症和其他血管生成依赖性疾病的抗血管生成治疗的有希望的新化合物。

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