Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Department of Operation, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Biomed Pharmacother. 2018 Jun;102:699-710. doi: 10.1016/j.biopha.2018.03.132. Epub 2018 Apr 5.
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.
神经胶质瘤是最常见的原发性恶性脑肿瘤，具有较高的代谢活性。针对代谢改变，特别是线粒体的靶向治疗，正在成为治疗癌症的有效方法。在这里，我们发现小檗碱，一种用作抗菌剂的天然化合物，可降低神经胶质瘤的细胞活力并诱导类似胀亡的死亡，其特征是细胞肿胀、细胞质空泡和质膜起泡，并且这些效应与细胞内三磷酸腺苷 (ATP) 耗竭有关。我们还发现，小檗碱诱导自噬作为一种保护作用，并降低耗氧率 (OCR)，通过抑制磷酸化细胞外调节蛋白激酶 (p-ERK1/2) 来抑制线粒体有氧呼吸。此外，小檗碱下调线粒体 p-ERK1/2 抑制有氧呼吸并导致糖酵解，这是一种低效的能量产生途径。此外，小檗碱在体内减少肿瘤生长并抑制 Ki-67 和 p-ERK1/2 的表达。结果表明，小檗碱抑制线粒体的有氧氧化并降低其能量产生效率，通过降低 ERK1/2 活性来降低代谢活性。
