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
2011 Impact Factor: 2.868
2011 SCImago Journal Rankings: 0.379
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
GrantsThe effects of berberine and its mechanism on angiogenesis in hepatocellular carcinoma in vitro and in vivo systems
The role of autophagy and mitochondrial apoptosis in berberine induced hepatocellular caricinoma cell death and its underlying mechanism
DC Field
Value
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.grantThe effects of berberine and its mechanism on angiogenesis in hepatocellular carcinoma in vitro and in vivo systems
dc.description.grantThe role of autophagy and mitochondrial apoptosis in berberine induced hepatocellular caricinoma cell death and its underlying mechanism
dc.description.grantcode99722
dc.description.grantcode101411
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.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
2011 Impact Factor: 2.868
2011 SCImago Journal Rankings: 0.379
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.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.rightsJournal of Cellular Biochemistry. Copyright © John Wiley & Sons, Inc.
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
Author Affiliations
  1. The University of Hong Kong