Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation

Cancer Cell International

Li-ming Shen¹  Lei Cheng¹  Hong-xin Jiang³  Bin Wang³  Zhi-qing Zhang²  Rong Yu¹ 

[1] Department of Interventional Radiology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China;Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China;Department of Oncology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China

关键词: Autophagy and mTOR;    Apoptosis;    AMPK;    Berberine;    Hepatocellular carcinoma;   

Others  :  791876
DOI  :  10.1186/1475-2867-14-49

 received in 2013-11-11, accepted in 2014-04-28,  发布年份 2014

【 摘 要 】

Background

Hepatocellular carcinoma (HCC), the primary liver cancer, is one of the most malignant human tumors with extremely poor prognosis. The aim of this study was to investigate the anti-cancer effect of berberine in a human hepatocellular carcinoma cell line (HepG2), and to study the underlying mechanisms by focusing on the AMP-activated protein kinase (AMPK) signaling cascade.

Results

We found that berberine induced both apoptotic and autophagic death of HepG2 cells, which was associated with a significant activation of AMPK and an increased expression of the inactive form of acetyl-CoA carboxylase (ACC). Inhibition of AMPK by RNA interference (RNAi) or by its inhibitor compound C suppressed berberine-induced caspase-3 cleavage, apoptosis and autophagy in HepG2 cells, while AICAR, the AMPK activator, possessed strong cytotoxic effects. In HepG2 cells, mammalian target of rapamycin complex 1 (mTORC1) activation was important for cell survival, and berberine inhibited mTORC1 via AMPK activation.

Conclusions

Together, these results suggested that berberine-induced both apoptotic and autophagic death requires AMPK activation in HepG2 cells.

【 授权许可】

   
2014 Yu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 1.

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