A New Strategy to Fight Metallodrug Resistance: Mitochondria-Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells.
Angew Chem Int Ed Engl
; 61(27): e202203843, 2022 07 04.
Article
em En
| MEDLINE
| ID: mdl-35384194
ABSTRACT
Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein-based cyclometalated IrIII 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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Mitofagia
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China