Published in:
Open Access
01-12-2014 | Primary research
Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation
Authors:
Rong Yu, Zhi-qing Zhang, Bin Wang, Hong-xin Jiang, Lei Cheng, Li-ming Shen
Published in:
Cancer Cell International
|
Issue 1/2014
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Abstract
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.