Berberine targets the electron transport chain complex I and re- veals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation

被引：9
|
作者：
Huang, Zhe [1 ,2 ]
Shen, Yunfu [1 ]
Liu, Wenjun [2 ]
Yang, Yan [1 ,2 ]
Guo, Ling [1 ,2 ]
Yan, Qin [2 ]
Wei, Chengming [1 ]
Guo, Qulian [2 ]
Fan, Xianming [3 ]
Ma, Wenzhe [1 ]
机构：
[1] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
[2] Southwest Med Univ, Sichuan Clin Res Ctr Birth Defects, Dept Pediat, Affiliated Hosp, Luzhou 646000, Peoples R China
[3] Southwest Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp, Luzhou 646000, Peoples R China
来源：
CHINESE JOURNAL OF NATURAL MEDICINES | 2023年 / 21卷 / 02期
关键词：
Berberine; Oxidative phosphorylation; Complex I; Mutant IDH1; Acute myeloid leukemia; OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL; CELLS; METABOLISM; INHIBITION; METFORMIN; INCREASE; MUSCLE; CYCLE; SITU;
D O I：
10.1016/S1875-5364(23)60391-7
中图分类号：
R [医药、卫生];
学科分类号：
10 ;
摘要：
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 biosyn-thetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epi-genetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berber-ine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) com-plex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileuk-emic effect in vitro and in 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.
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页码：136 / 145
页数：10
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