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Article: Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells

TitleBerberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells
Authors
KeywordsApoptosis
Berberine
Cell migration
G2 arrest
Rho GTPases
Issue Date2009
PublisherDemetrios A Spandidos Ed & Pub. The Journal's web site is located at http://147.52.72.117/IJMM/ijmm.htm
Citation
International Journal Of Molecular Medicine, 2009, v. 24 n. 1, p. 131-138 How to Cite?
AbstractBerberine is an active ingredient extracted from Coptidis rhizoma which has been used for centuries as a traditional Chinese medicine for treatment of inflammatory diseases. Recent studies have indicated that berberine has anticancer properties. Berberine arrested cell growth and inhibited cell migration in various cancer cell lines. In this study, we examined the effects of berberine on HONE1 cells, which have been commonly used as a cell model for naso-pharyngeal carcinoma. We observed the inhibitory effects of berberine on HONE1 cells at a high dosage (>150 μM). Berberine effectively induced the mitotic arrest of HONE1 cells at 300 μM which was associated with apoptosis. Berberine had differential intracellular localization at low and high doses. At a low dose (50 μM), berberine was localized in the mitochondria while at a high dose (300 μM), berberine was localized in the nucleus which may have induced mitotic arrest. Berberine effectively inhibited cell migration and invasion at low doses. Using a specific GST pull-down assay of activated Rho GTPases, we demonstrated that berberine suppressed the activation of Rho GTPases including RhoA, Cdc42 and Rac1. This indicates a novel function of berberine in the suppression of Rho GTPase signaling to mediate its inhibitory action on cell migration and motility. The potential of berberine to inhibit cancer metastasis in cancer warrants further investigation.
Persistent Identifierhttp://hdl.handle.net/10722/67516
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 1.167
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong10206540
10208005
The University Grant Committee (UGC) of Hong Kong SAR of China764708M
UGC-Matching Grant Scheme20740314
Funding Information:

The study was financially supported by grants from the research council of the University of Hong Kong (Project codes: 10206540 and 10208005), The University Grant Committee (UGC) of Hong Kong SAR of China (Project Code: 764708M), UGC-Matching Grant Scheme (4th Phase, Project Code: 20740314) and Pong Ding Yueng Endowment Fund for Education & Research in Chinese-Western Medicine (Project code: 20005274). The authors are grateful to the support of the Faculty Core Imaging Facility and would like to express thanks to Mr. Tony Chan and Ms. Alla Li for their help with the confocal microscope study.

References

 

DC FieldValueLanguage
dc.contributor.authorTsang, CMen_HK
dc.contributor.authorLau, EPWen_HK
dc.contributor.authorDi, Ken_HK
dc.contributor.authorCheung, PYen_HK
dc.contributor.authorHau, PMen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorCheung, ALMen_HK
dc.contributor.authorWan, TSKen_HK
dc.contributor.authorTong, Yen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorFeng, Yen_HK
dc.date.accessioned2010-09-06T05:55:49Z-
dc.date.available2010-09-06T05:55:49Z-
dc.date.issued2009en_HK
dc.identifier.citationInternational Journal Of Molecular Medicine, 2009, v. 24 n. 1, p. 131-138en_HK
dc.identifier.issn1107-3756en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67516-
dc.description.abstractBerberine is an active ingredient extracted from Coptidis rhizoma which has been used for centuries as a traditional Chinese medicine for treatment of inflammatory diseases. Recent studies have indicated that berberine has anticancer properties. Berberine arrested cell growth and inhibited cell migration in various cancer cell lines. In this study, we examined the effects of berberine on HONE1 cells, which have been commonly used as a cell model for naso-pharyngeal carcinoma. We observed the inhibitory effects of berberine on HONE1 cells at a high dosage (>150 μM). Berberine effectively induced the mitotic arrest of HONE1 cells at 300 μM which was associated with apoptosis. Berberine had differential intracellular localization at low and high doses. At a low dose (50 μM), berberine was localized in the mitochondria while at a high dose (300 μM), berberine was localized in the nucleus which may have induced mitotic arrest. Berberine effectively inhibited cell migration and invasion at low doses. Using a specific GST pull-down assay of activated Rho GTPases, we demonstrated that berberine suppressed the activation of Rho GTPases including RhoA, Cdc42 and Rac1. This indicates a novel function of berberine in the suppression of Rho GTPase signaling to mediate its inhibitory action on cell migration and motility. The potential of berberine to inhibit cancer metastasis in cancer warrants further investigation.en_HK
dc.languageengen_HK
dc.publisherDemetrios A Spandidos Ed & Pub. The Journal's web site is located at http://147.52.72.117/IJMM/ijmm.htmen_HK
dc.relation.ispartofInternational Journal of Molecular Medicineen_HK
dc.subjectApoptosisen_HK
dc.subjectBerberineen_HK
dc.subjectCell migrationen_HK
dc.subjectG2 arresten_HK
dc.subjectRho GTPasesen_HK
dc.subject.meshAntineoplastic Agents - pharmacologyen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshBerberine - administration & dosage - pharmacologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Movement - drug effectsen_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshG2 Phase - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshNasopharyngeal Neoplasmsen_HK
dc.subject.meshNeoplasm Invasivenessen_HK
dc.subject.meshNeoplasm Metastasisen_HK
dc.subject.meshPlant Extracts - pharmacologyen_HK
dc.subject.meshrho GTP-Binding Proteins - antagonists & inhibitors - metabolismen_HK
dc.titleBerberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1107-3756&volume=24&spage=131&epage=138&date=2009&atitle=Berberine+inhibits+Rho+GTPases+and+cell+migration+at+low+doses+but+induces+G2+arrest+and+apoptosis+at+high+doses+in+human+cancer+cellsen_HK
dc.identifier.emailChing, YP: ypching@hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.emailTong, Y: tongyao@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.emailFeng, Y: yfeng@hku.hken_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.identifier.authorityTong, Y=rp00509en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityFeng, Y=rp00466en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.3892/ijmm_00000216en_HK
dc.identifier.pmid19513545-
dc.identifier.scopuseid_2-s2.0-67649515350en_HK
dc.identifier.hkuros164197en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649515350&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue1en_HK
dc.identifier.spage131en_HK
dc.identifier.epage138en_HK
dc.identifier.isiWOS:000267230900019-
dc.publisher.placeGreeceen_HK
dc.identifier.scopusauthoridTsang, CM=24831236400en_HK
dc.identifier.scopusauthoridLau, EPW=7103086020en_HK
dc.identifier.scopusauthoridDi, K=14526710900en_HK
dc.identifier.scopusauthoridCheung, PY=14024149900en_HK
dc.identifier.scopusauthoridHau, PM=14060079200en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK
dc.identifier.scopusauthoridWan, TSK=25623981600en_HK
dc.identifier.scopusauthoridTong, Y=9045384000en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridFeng, Y=24467969600en_HK
dc.identifier.issnl1107-3756-

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