title: Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation.
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.
authors.affiliation: Department of Oncology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China ; Department of Interventional Radiology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oncology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Jiang
authors.affiliation: Department of Interventional Radiology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Interventional Radiology, Suzhou Municipal Hospital, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Shen
keywords: AMPK; Apoptosis; Autophagy and mTOR; Berberine; Hepatocellular carcinoma