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

TitleBerberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanism
Authors
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
Citation
Journal of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/127611
ISSN
2023 Impact Factor: 3.0
2023 SCImago Journal Rankings: 0.768
ISI Accession Number ID
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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWang, Nen_HK
dc.contributor.authorFeng, Yen_HK
dc.contributor.authorZhu, Men_HK
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorTong, Yen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-10-31T13:35:33Z-
dc.date.available2010-10-31T13:35:33Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal of Cellular Biochemistry, 2010, v. 111 n. 6, p. 1426-1436en_HK
dc.identifier.issn0730-2312en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127611-
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.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503en_HK
dc.relation.ispartofJournal of Cellular Biochemistryen_HK
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.subjectapoptosisen_HK
dc.subjectautophagyen_HK
dc.subjectBcl-2/Beclin-1en_HK
dc.subjectberberineen_HK
dc.subjectmTORen_HK
dc.titleBerberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: The cellular mechanismen_HK
dc.typeArticleen_HK
dc.identifier.emailFeng, Y: yfeng@hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailTong, Y: tongyao@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.authorityFeng, Y=rp00466en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityTong, Y=rp00509en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturepreprint-
dc.identifier.doi10.1002/jcb.22869en_HK
dc.identifier.pmid20830746-
dc.identifier.scopuseid_2-s2.0-78649775152en_HK
dc.identifier.hkuros183036en_HK
dc.identifier.hkuros191226-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78649775152&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume111en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1426en_HK
dc.identifier.epage1436en_HK
dc.identifier.eissn1097-4644-
dc.identifier.isiWOS:000286300700005-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectThe effects of berberine and its mechanism on angiogenesis in hepatocellular carcinoma in vitro and in vivo systems-
dc.relation.projectThe role of autophagy and mitochondrial apoptosis in berberine induced hepatocellular caricinoma cell death and its underlying mechanism-
dc.identifier.scopusauthoridWang, N=35072317700en_HK
dc.identifier.scopusauthoridFeng, Y=24467969600en_HK
dc.identifier.scopusauthoridZhu, M=36706949300en_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridTong, Y=9045384000en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.issnl0730-2312-

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