Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice

Authors: Wang, Guan-Yu¹; Lv, Qing-Hua²; Dong, Qi²; Xu, Rong-Zhen²; Dong, Qing-Hua²

Source: Journal of Asian Natural Products Research, Volume 11, Number 3, March 2009 , pp. 219-228(10)

Publisher: Taylor and Francis Ltd

Abstract:

Berbamine, a natural compound from the plant Berberis amurensis, is a traditional Chinese medicine mainly used in stimulating normal hematopoiesis in clinic. Our previous studies demonstrated that berbamine has anti-leukemia activity. In this study, we investigated the anticancer activity of berbamine against human hepatocellular carcinoma (HCC) HepG2 cells in vitro and in vivo. Berbamine treatment decreased the cell growth in a dose-dependent manner with an IC50 value of 34.5 ± 0.5 μM. Flow cytometric analysis of apoptosis using Annexin V/propidium iodide staining showed that the percentage of apoptotic cells was increased in a time-dependent manner. Berbamine treatment increased the expression level of Fas and P53, caused depolarization of mitochondrial membrane and decrease of membrane potential, and activated caspase-3, -8, and -9 in HepG2 cells. Berbamine-induced apoptosis could be blocked by the broad caspase inhibitor z-VAD-fmk. HepG2 human HCC xenograft mice treated with berbamine showed a significant reduction in tumor growth rates compared to saline-treated mice. These studies suggest that berbamine exerts anticancer effects on human HCC HepG2 cells in vivo and in vitro, the induction of p53 and the activity of the Fas apoptotic system may participate in the anticancer activity of berbamine in HepG2 cells.

Keywords: berbamine; apoptosis; Fas; P53; caspase; hepatocellular carcinoma

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10286020802675076

Affiliations: 1: Department of Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China 2: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Hangzhou, China,Cancer Institute, the Second Affiliated Hospital of Zhejiang University, School o

Publication date: 2009-03-01

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