4.8 Article

A New Strategy to Fight Metallodrug Resistance: Mitochondria-Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells

期刊

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202203843

关键词

Iridium; Metabolic Adaptation; Metallodrug Resistance; Mitochondria-Targeting; Mitophagy

资金

  1. NSFC [21771109, 21778033, 21977052]
  2. Special Appointed Professorship of Jiangsu Province

向作者/读者索取更多资源

A new cyclometalated Ir-III complex, Ir-Rhein, based on rhein, is reported to specifically target mitochondria and effectively inhibit metabolic adaptations. The complex induces severe mitochondrial damage and initiates mitophagy, leading to reduction in both mitochondrial and glycolytic bioenergetics and eventually causing ATP starvation death. Moreover, Ir-Rhein overcomes cisplatin resistance and shows promising antiproliferation performance for cisplatin-resistant cancer cells.
Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein-based cyclometalated Ir-III complex, Ir-Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir-Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death. Moreover, Ir-Rhein can overcome cisplatin resistance. Co-incubation experiment, 3D tumor spheroids experiment and transcriptome analysis reveal that Ir-Rhein shows promising antiproliferation performance for cisplatin-resistant cancer cells with the regulation of platinum resistance-related transporters. To our knowledge, this is a new strategy to overcome metallodrug resistance with a mitochondria-relevant treatment.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据