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Article: Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
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TitleBerberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
 
AuthorsWang, N1
Feng, Y1
Zhu, M1
Tsang, CM1
Man, K1
Tong, Y1
Tsao, SW1
 
Keywordsapoptosis
autophagy
Bcl-2/Beclin-1
berberine
mTOR
 
Issue Date2010
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503
 
CitationJournal Of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jcb.22869
 
AbstractExtensive 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.
 
ISSN0730-2312
2013 Impact Factor: 3.368
 
DOIhttp://dx.doi.org/10.1002/jcb.22869
 
ISI Accession Number IDWOS:000286300700005
Funding AgencyGrant Number
Research Council of the University of Hong Kong200811159197
200907176140
Research Grants Council of Hong KongHKU764708M
Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine20005274
Hong Kong Government20740314
Funding Information:

Grant sponsor: The Research Council of the University of Hong Kong; Grant number: 200811159197 200907176140; Grant sponsor: The Research Grants Council of Hong Kong; Grant number: HKU764708M; Grant sponsor: Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine; Grant number: 20005274; Grant sponsor: Hong Kong Government Matching Grant Scheme; Grant number: 20740314.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWang, N
 
dc.contributor.authorFeng, Y
 
dc.contributor.authorZhu, M
 
dc.contributor.authorTsang, CM
 
dc.contributor.authorMan, K
 
dc.contributor.authorTong, Y
 
dc.contributor.authorTsao, SW
 
dc.date.accessioned2010-10-31T13:35:33Z
 
dc.date.available2010-10-31T13:35:33Z
 
dc.date.issued2010
 
dc.description.abstractExtensive 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.
 
dc.description.naturepostprint
 
dc.identifier.citationJournal Of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jcb.22869
 
dc.identifier.doihttp://dx.doi.org/10.1002/jcb.22869
 
dc.identifier.eissn1097-4644
 
dc.identifier.epage1436
 
dc.identifier.hkuros183036
 
dc.identifier.isiWOS:000286300700005
Funding AgencyGrant Number
Research Council of the University of Hong Kong200811159197
200907176140
Research Grants Council of Hong KongHKU764708M
Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine20005274
Hong Kong Government20740314
Funding Information:

Grant sponsor: The Research Council of the University of Hong Kong; Grant number: 200811159197 200907176140; Grant sponsor: The Research Grants Council of Hong Kong; Grant number: HKU764708M; Grant sponsor: Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine; Grant number: 20005274; Grant sponsor: Hong Kong Government Matching Grant Scheme; Grant number: 20740314.

 
dc.identifier.issn0730-2312
2013 Impact Factor: 3.368
 
dc.identifier.issue6
 
dc.identifier.openurl
 
dc.identifier.pmid20830746
 
dc.identifier.scopuseid_2-s2.0-78649775152
 
dc.identifier.spage1426
 
dc.identifier.urihttp://hdl.handle.net/10722/127611
 
dc.identifier.volume111
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Cellular Biochemistry
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Cellular Biochemistry. Copyright © John Wiley & Sons, Inc.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.rightsThis is a preprint of an article published in Journal of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436
 
dc.subjectapoptosis
 
dc.subjectautophagy
 
dc.subjectBcl-2/Beclin-1
 
dc.subjectberberine
 
dc.subjectmTOR
 
dc.titleBerberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong