在 ((VI) 化物复合体上的双酸连接体控制细胞内向和细胞死亡途径
Kogularamanan Suntharalingam1, Timothy C Johnstone, Peter M Bruno
1Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|September 18, 2013
概括
抗增殖的化合物显示可调节的细胞反应. 复合体4中的配体修饰会诱导细胞内膜网膜应激和癌细胞中的p53-独立的亡.
科学领域:
- 无机化学 无机化学
- 癌症生物学 癌症生物学
- 细胞应激反应的应激反应
背景情况:
- 抗增殖的 () 化物化合物 (OsN () N^N) Cl3) 正在用于癌症治疗的研究中.
- 这些合物复合物的连接物修饰可以改变它们的生物活性.
研究的目的:
- 为了研究 () 化物化合物与各种配体的细胞反应.
- 了解化合物在癌细胞中的作用机制.
主要方法:
- 用不同的N^N配体合成和表征 (VI) 化物化合物.
- 细胞测试以评估DNA损伤,细胞周期进展和细胞亡.
- 分析与p53通路相关的蛋白质表达和未折叠的蛋白质反应.
主要成果:
- 复杂2诱导的DNA损伤,p53通路的激活,G2/M细胞周期的停止,和卡斯帕酶依赖的亡.
- 复杂4诱导的内等质网膜 (ER) 应激,展开的蛋白质反应 (UPR) 途径激活,和p53独立的亡.
- 化合物4是第一个报告的化合物,可在癌细胞中诱导ER压力.
结论:
- 在 () 化物化合物中微妙的连接物修饰可以精确调整细胞反应.
- 奥斯复合物4通过诱导ER压力介导的亡,代表了一种新的治疗策略.
- 对用于癌症治疗的基化合物的进一步研究是有必要的.
相关概念视频
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