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Biomed Pharmacother. 2018 Jun;102:699-710. doi: 10.1016/j.biopha.2018.03.132. Epub 2018 Apr 5.

Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas.

Author information

1
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
2
Department of Operation, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
3
Department of Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
4
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. Electronic address: cy_9201982@aliyun.com.
5
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. Electronic address: huanghy@jlu.edu.cn.

Abstract

Gliomas, the most common primary malignant brain tumor, exhibit high metabolic activity. The targeting of metabolism alterations, particularly in mitochondria, is emerging as an efficient approach for curing cancers. Here, we showed that berberine, a natural compound that is used as an antibacterial agent, could reduce cellular viability and induce oncosis-like death, characterized by cell swelling, cytoplasmic vacuoles and plasma membrane blebbing, in gliomas, and that these effects were correlated with intracellular adenosine triphosphate (ATP) depletion. We also found that berberine induced autophagy as a protective effect and decreased the oxygen consumption rate (OCR), which could inhibit mitochondrial aerobic respiration by repressing phosphorylated extracellular regulated protein kinases (p-ERK1/2). Furthermore, the down-regulation of mitochondrial p-ERK1/2 by berberine inhibited aerobic respiration and led to glycolysis, an inefficient energy production pathway. In addition, berberine reduced tumor growth and inhibited Ki-67 and p-ERK1/2 expression in vivo. The results demonstrate that berberine, which represses aerobic oxidation in mitochondria and decreases their energy production efficiency, decreases metabolic activity by reducing ERK1/2 activity.

KEYWORDS:

ATP; Berberine; ERK1/2; Glioma; Oncosis

PMID:
29604589
DOI:
10.1016/j.biopha.2018.03.132
[Indexed for MEDLINE]

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