Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation.
10.1016/S1875-5364(23)60391-7
- Author:
Zhe HUANG
1
,
2
;
Yunfu SHEN
3
;
Wenjun LIU
4
;
Yan YANG
4
;
Ling GUO
4
;
Qin YAN
4
;
Chengming WEI
3
;
Qulian GUO
4
;
Xianming FAN
5
;
Wenzhe MA
6
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China
2. Department of Pediatrics, the Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou 646000, China.
3. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China.
4. Department of Pediatrics, the Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou 646000, China.
5. Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China. Electronic address: fxm129120@sina.com.
6. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China. Electronic address: wzma@must.edu.mo.
- Publication Type:Journal Article
- Keywords:
Acute myeloid leukemia;
Berberine;
Complex I;
Mutant IDH1;
Oxidative phosphorylation
- MeSH:
Humans;
Oxidative Phosphorylation;
Berberine;
Electron Transport;
Mitochondria;
Leukemia, Myeloid, Acute;
Isocitrate Dehydrogenase
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(2):136-145
- CountryChina
- Language:English
-
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.
