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

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

  • Biomed Pharmacother. 2018 Jun;102:699-710. doi: 10.1016/j.biopha.2018.03.132.
Yuxue Sun 1 Jing Yu 2 Xinrui Liu 1 Chaochao Zhang 1 Junguo Cao 1 Guihong Li 1 Xingxing Liu 3 Yong Chen 4 Haiyan Huang 5
Affiliations

Affiliations

  • 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: [email protected].
  • 5 Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. Electronic address: [email protected].
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.

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