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Article

Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma

  • Authors:
    • Xiaolong Yang
    • Ning Huang
  • View Affiliations / Copyright

    Affiliations: Research Unit of Infection and Immunity, Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
  • Pages: 505-510
    |
    Published online on: May 31, 2013
       https://doi.org/10.3892/mmr.2013.1506
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Abstract

Advanced hepatocellular carcinoma (HCC) is insensitive to traditional chemotherapeutic approaches, which causes difficulty in the development of novel agents for the treatment of HCC. Berberine is the main component of Coptidis Rhizoma, a plant alkaloid with a long history of use in Chinese medicine, and has become a potential candidate for the treatment of HCC due to its high antitumor activity and low toxicity. In this study, we investigated the mechanism via which berberine exerts its inhibitory effects on HCC. The data demonstrated that berberine selectively decreased cell viability in a time‑ and dose‑dependent manner in the HepG2, SMMC‑7721 and Bel‑7402 HCC cell lines compared with normal hepatocytes (HL‑7702 cells), as determined by a sulforhodamine B assay. Flow cytometric analysis revealed that berberine increased the number of late apoptotic cells. Pretreatment with berberine in HepG2 cells resulted in a significant increase in phosphorylated AMP‑activated protein kinase (AMPK), as well as a marked elevation in phosphorylated Akt levels. In addition, the activation of AMPK was accompanied by apoptotic effects that occurred in a caspase‑dependent manner through the mitochondrial pathway, and was coupled with the release of cytochrome c from the mitochondria and the activation of caspase‑9 and ‑3. Furthermore, the ratio of Bax/Bcl‑2 was increased in a dose‑dependent manner. Our study supports the theory that berberine selectively inhibits the growth of human hepatocellular cancer cells by inducing AMPK‑mediated caspase‑dependent mitochondrial pathway cell apoptosis, and rarely causes cytotoxicity in normal cells. Therefore, berberine is a promising novel agent for the treatment of HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Yang X and Huang N: Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma. Mol Med Rep 8: 505-510, 2013.
APA
Yang, X., & Huang, N. (2013). Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma. Molecular Medicine Reports, 8, 505-510. https://doi.org/10.3892/mmr.2013.1506
MLA
Yang, X., Huang, N."Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma". Molecular Medicine Reports 8.2 (2013): 505-510.
Chicago
Yang, X., Huang, N."Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma". Molecular Medicine Reports 8, no. 2 (2013): 505-510. https://doi.org/10.3892/mmr.2013.1506
Copy and paste a formatted citation
x
Spandidos Publications style
Yang X and Huang N: Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma. Mol Med Rep 8: 505-510, 2013.
APA
Yang, X., & Huang, N. (2013). Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma. Molecular Medicine Reports, 8, 505-510. https://doi.org/10.3892/mmr.2013.1506
MLA
Yang, X., Huang, N."Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma". Molecular Medicine Reports 8.2 (2013): 505-510.
Chicago
Yang, X., Huang, N."Berberine induces selective apoptosis through the AMPK‑mediated mitochondrial/caspase pathway in hepatocellular carcinoma". Molecular Medicine Reports 8, no. 2 (2013): 505-510. https://doi.org/10.3892/mmr.2013.1506
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