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Article: Proteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinoma

TitleProteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinoma
Authors
KeywordsDrug target
Gambogic acid
Hepatocellular carcinoma
Proteomics
Stathmin
Issue Date2009
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/proteomics
Citation
Proteomics, 2009, v. 9 n. 2, p. 242-253 How to Cite?
AbstractGamboge has been developed as an injectable drug for cancer treatment in China. In this study, the inhibition ratio and their IC 50 values of two derivatives from Gamboge in hepatocellular carcinoma (HCC) were determined. Proteomic approach was employed to reveal the target proteins of these two derivatives, gambogic acid (GA), and gambogenic acid (GEA). HCC cells were cultured under varied conditions with the addition of either GA or GEA. Twenty differentially expressed proteins were identified and the four most distinctly expressed proteins were further validated by Western blotting. GA and GEA revealed inhibitory effects on HCC cell proliferation. The expression of cyclin-dependent kinase 4 inhibitor A and guanine nucleotide-binding protein β subunit 1 were upregulated by both xanthones, whilst the expression of 14-3-3 protein sigma and stathmin 1 (STMN1) were downregulated. Furthermore, overexpression of STMN1 in HCC cells decreased their sensitivity, whilst small interfering RNAs targeting STMN1 enhanced their sensitivity to GA and GEA. In conclusion, our study suggested for the first time that STMN1 might be a major target for GA and GEA in combating HCC. Further investigation may lead to a new generation of anticancer drugs exerting synergistic effect with conventional therapy, thus to promote treatment efficacy. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA.
Persistent Identifierhttp://hdl.handle.net/10722/58405
ISSN
2015 Impact Factor: 4.079
2015 SCImago Journal Rankings: 1.476
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_HK
dc.contributor.authorChen, Yen_HK
dc.contributor.authorHan, QBen_HK
dc.contributor.authorChan, CYen_HK
dc.contributor.authorWang, Hen_HK
dc.contributor.authorLiu, Zen_HK
dc.contributor.authorCheng, CHKen_HK
dc.contributor.authorYew, DTen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorHe, MLen_HK
dc.contributor.authorXu, HXen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorKung, HFen_HK
dc.date.accessioned2010-05-31T03:29:43Z-
dc.date.available2010-05-31T03:29:43Z-
dc.date.issued2009en_HK
dc.identifier.citationProteomics, 2009, v. 9 n. 2, p. 242-253en_HK
dc.identifier.issn1615-9853en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58405-
dc.description.abstractGamboge has been developed as an injectable drug for cancer treatment in China. In this study, the inhibition ratio and their IC 50 values of two derivatives from Gamboge in hepatocellular carcinoma (HCC) were determined. Proteomic approach was employed to reveal the target proteins of these two derivatives, gambogic acid (GA), and gambogenic acid (GEA). HCC cells were cultured under varied conditions with the addition of either GA or GEA. Twenty differentially expressed proteins were identified and the four most distinctly expressed proteins were further validated by Western blotting. GA and GEA revealed inhibitory effects on HCC cell proliferation. The expression of cyclin-dependent kinase 4 inhibitor A and guanine nucleotide-binding protein β subunit 1 were upregulated by both xanthones, whilst the expression of 14-3-3 protein sigma and stathmin 1 (STMN1) were downregulated. Furthermore, overexpression of STMN1 in HCC cells decreased their sensitivity, whilst small interfering RNAs targeting STMN1 enhanced their sensitivity to GA and GEA. In conclusion, our study suggested for the first time that STMN1 might be a major target for GA and GEA in combating HCC. Further investigation may lead to a new generation of anticancer drugs exerting synergistic effect with conventional therapy, thus to promote treatment efficacy. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA.en_HK
dc.languageengen_HK
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/proteomicsen_HK
dc.relation.ispartofProteomicsen_HK
dc.subjectDrug targeten_HK
dc.subjectGambogic aciden_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectProteomicsen_HK
dc.subjectStathminen_HK
dc.titleProteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1615-9853&volume=9&issue=2&spage=242&epage=253&date=2008&atitle=Proteomic+Identification+of+Molecular+Targets+of+Gambogic+Acid:+Role+of+Stathmin+in+Hepatocellular+Carcinomaen_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/pmic.200800155en_HK
dc.identifier.pmid19086098-
dc.identifier.scopuseid_2-s2.0-60349092524en_HK
dc.identifier.hkuros154153en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-60349092524&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume9en_HK
dc.identifier.issue2en_HK
dc.identifier.spage242en_HK
dc.identifier.epage253en_HK
dc.identifier.isiWOS:000263117600003-
dc.publisher.placeGermanyen_HK
dc.identifier.scopusauthoridWang, X=35235704600en_HK
dc.identifier.scopusauthoridChen, Y=24075600300en_HK
dc.identifier.scopusauthoridHan, QB=7202485341en_HK
dc.identifier.scopusauthoridChan, CY=22033276600en_HK
dc.identifier.scopusauthoridWang, H=8443997400en_HK
dc.identifier.scopusauthoridLiu, Z=36066691200en_HK
dc.identifier.scopusauthoridCheng, CHK=7404798014en_HK
dc.identifier.scopusauthoridYew, DT=7007034694en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridHe, ML=35080389700en_HK
dc.identifier.scopusauthoridXu, HX=7407449416en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK

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