Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
; (6): 136-145, 2023.
Article
em En
| WPRIM
| ID: wpr-971668
Biblioteca responsável:
WPRO
ABSTRACT
Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Fosforilação Oxidativa
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Berberina
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Leucemia Mieloide Aguda
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Transporte de Elétrons
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Isocitrato Desidrogenase
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Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Chinese Journal of Natural Medicines (English Ed.)
Ano de publicação:
2023
Tipo de documento:
Article