Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells.
Sci Rep
; 13(1): 22383, 2023 12 16.
Article
en En
| MEDLINE
| ID: mdl-38104159
ABSTRACT
Artesunate is a derivative of artemisinin, an active compound isolated from Artemisia annua which has been used in Traditional Chinese Medicine and to treat malaria worldwide. Artemisinin derivatives have exhibited anti-cancer activity against both solid tumors and leukemia. The direct target(s) of artesunate are controversial; although, heme-bound proteins in the mitochondria have been implicated. We utilized computational modeling to calculate the predicted binding score of artesunate with heme-bound mitochondrial proteins and identified cytochrome c as potential artesunate target. UV-visible spectroscopy showed changes in the absorbance spectrum, and thus protein structure, when cytochrome c was incubated with artesunate. Artesunate induces apoptosis, disrupts mitochondrial membrane potential, and is antagonized by methazolamide in pediatric AML cells indicating a probable mechanism of action involving cytochrome c. We utilized a multi-disciplinary approach to show that artesunate can interact with and is dependent on cytochrome c release to induce cell death in pediatric AML cell lines.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Artemisininas
/
Antimaláricos
Límite:
Child
/
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos