Mitochondria play an important role in the cell proliferation suppressing activity of berberine.
After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism.
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xiao-Jin
XJ
Yan
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xuan
X
Yu
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xin-Pei
XP
Wang
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Jing-Fei
JF
Jiang
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Zhi-Yi
ZY
Yuan
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Xi
X
Lu
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Fan
F
Lei
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Dong-Ming
DM
Xing
D001599:Berberine / Q000494:pharmacology*; D002087:Butyrates / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D004272:DNA, Mitochondrial; D004305:Dose-Response Relationship, Drug; D018628:Gene Dosage; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D009243:NAD / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism
D002087:Butyrates; D004272:DNA, Mitochondrial; D001599:Berberine; D009243:NAD; C005087:alpha-ketobutyric acid; D019289:Pyruvic Acid