探索单核和双核DNA光开关复合体的细胞毒性,摄取,细胞反应和蛋白质组学
Paul J Jarman1, Felicity Noakes1,2, Simon Fairbanks2
1Department of Biomedical Science , University of Sheffield , Sheffield S10 2TN , U.K.
Journal of the American Chemical Society
|January 1, 2019
概括
新的金属复合物显示出作为抗癌治疗的希望. 这些化合物通过瘤,而不是细胞亡来诱导细胞快速死亡,为抗药性瘤提供了一种新的治疗策略.
科学领域:
- 协调化学 协调化学
- 化学生物学 化学生物学
- 癌症研究 癌症研究
背景情况:
- 对基化疗的药物耐药性是一个主要的临床挑战,通常与亡逃避有关.
- 金属复合物提供了其他抗癌策略,特别是与DNA相互作用的抗癌策略.
- 了解新型药物诱导的细胞死亡机制对于治疗开发至关重要.
研究的目的:
- 为了比较具有不同结构的新型复合物的DNA结合模式和细胞毒性作用.
- 研究由这些复杂物诱导的细胞死亡机制,特别是在抗癌细胞中.
- 探索这些复合物的潜力,作为新的化疗药物的来源.
主要方法:
- 单核和双核复合物的合成和表征.
- 评估DNA相互作用模式 (间隙与沟结合) 和细胞毒性.
- 活细胞显微镜利用光开关效应来监测细胞死亡时间.
- 定量蛋白质组分析以确定受复杂物影响的细胞通路.
主要成果:
- 结构性修改将DNA结合从间接转移到沟结合,降低功效,但没有克服白金电阻.
- 所有的复杂物都通过瘤病引起了细胞快速死亡,绕过了典型的亡途径.
- 蛋白质组分析揭示了与氧化应激和DNA修复相关的细胞反应.
结论:
- 对于这些复合物来说,DNA结合模式并不是抗性的主要因素.
- 瘤炎诱导是一种用于癌症治疗的新型非亡性细胞死亡机制.
- 这些复合体是开发抗抗癌新型化疗药物的有希望的线索.
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