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Title: Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
Authors: Feng, Y;Man, K;Tong, Y;Tsao, SW;Wang, N;Zhu, M;Tsang, CM
subject: Apoptosis;autophagy;Bcl-2/Beclin-1;berberine;mTOR
Year: 2010
Publisher: John Wiley & Sons, Inc. The Journal's web site is located at
United States
Description: Extensive studies have revealed that berberine, a small molecule derived from Coptidis rhizoma (Huanglian in Chinese) and many other plants, has strong anti-tumor properties. To better understand berberine-induced cell death and its underlying mechanisms in cancer, we examined autophagy and apoptosis in the human hepatic carcinoma cell lines HepG2 and MHCC97-L. The results of this study indicate that berberine can induce both autophagy and apoptosis in hepatocellular carcinoma cells. Berberine-induced cell death in human hepatic carcinoma cells was diminished in the presence of the cell death inhibitor 3-methyladenine, or following interference with the essential autophagy gene Atg5. Mechanistic studies showed that berberine may activate mitochondrial apoptosis in HepG2 and MHCC97-L cells by increasing Bax expression, the formation of permeable transition pores, cytochrome C release to cytosol, and subsequent activation of the caspases 3 and 9 execution pathway. Berberine may also induce autophagic cell death in HepG2 and MHCC97-L cells through activation of Beclin-1 and inhibition of the mTOR-signaling pathway by suppressing the activity of Akt and up-regulating P38 MAPK signaling. This is the first study to describe the role of Beclin-1 activation and mTOR inhibition in berberine-induced autophagic cell death. These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms. © 2010 Wiley-Liss, Inc.
Standard no: Journal Of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436
Appears in Collections:Department of Anatomy

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