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Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism

Wang, Ning, Feng, Yibin, Zhu, Meifen, Tsang, Chi‐Man, Man, Kwan, Tong, Yao, Tsao, Sai‐Wah·2010·Journal of Cellular Biochemistry

DOI 10.1002/jcb.22869

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Abstract

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. J. Cell. Biochem. 111: 1426–1436, 2010. © 2010 Wiley‐Liss, Inc.

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Authors: Wang, N., Feng, Y., Zhu, M., Tsang, C., Man, K., Tong, Y., & Tsao, S.
Venue: Journal of Cellular Biochemistry
Publisher: Wiley
Published: 2010-11-29
Volume: 111
Issue: 6
Pages: 1426-1436
ISSN: 0730-2312 (ISSN-L)
1097-4644
DOI: 10.1002/jcb.22869
OpenAlex: W2074310251
Cited by: 289
References: 47
FWCI: 8.81
Type: journal article
Language: en
Open access: closed

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Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism

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