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Article: Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

TitleInhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition
Authors
KeywordsAkt
Apoptosis
Caspases
Gold(III) porphyrin 1a
Neuroblastoma
Issue Date2009
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 2009, v. 101 n. 2, p. 342-349 How to Cite?
AbstractBackground:Gold(III) porphyrin 1a is a new class of anticancer drug, which inhibits cell proliferation of wide range of human cancer cell lines and induces apoptosis in human nasopharyngeal carcinoma cells. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells.Methods:Cell proliferation and apoptosis were determined by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V binding, respectively. Western blot assay was used to detect proteins involved in apoptotic and Akt pathways. In vivo tumour growth was assessed by inoculating tumour cells to nude mice subcutaneously, and gold(III) porphyrin 1a was administrated intravenously.Results:This study assessed the antitumour effect and mechanism of gold(III) porphyrin 1a on neuroblastoma in vitro and in vivo. Gold(III) porphyrin 1a displayed a growth inhibition and induction of apoptosis in neuroblastoma cells effectively in vitro, which was accompanied with release of cytochrome c and Smac/DIABLO and caspases activation. Further studies indicated that gold(III) porphyrin 1a inhibited X-linked inhibitor of apoptosis (XIAP). However, we found that gold(III) porphyrin 1a can induce a survival signal, Akt activation within minutes and could last for at least 24 h. To further confirm association between activation of Akt and the effectiveness of gold(III) porphyrin 1a, neuroblastoma cells were treated with API-2, an Akt-specific inhibitor. API-2 sensitised cells to gold(III) porphyrin 1a-induced apoptosis and growth inhibition.Conclusion:These results suggested that Akt may be considered as a molecular brake that neuroblastoma cells rely on to slow down gold(III) porphyrin 1a-induced apoptosis and antiproliferation. Gold(III) porphyrin 1a is a mitochondrial apoptotic stimulus but also activates Akt, suggesting an involvement of Akt in mediating the effectiveness to growth inhibition and apoptosis by gold(III) porphyrin 1a and that inhibition of Akt can enhance the anticancer activity of gold(III) porphyrin 1a in neuroblastoma. © 2009 Cancer Research UK.
Persistent Identifierhttp://hdl.handle.net/10722/69512
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7250/02M
National Science FoundationDMS0714589
Funding Information:

This study was supported by Hong Kong Research Grants Council (HKU7250/02M) and National Science Foundation (DMS0714589).

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Wen_HK
dc.contributor.authorXie, Yen_HK
dc.contributor.authorSun, RWYen_HK
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorYoung, Jen_HK
dc.contributor.authorYu, WYen_HK
dc.contributor.authorChe, CMen_HK
dc.contributor.authorTam, PKen_HK
dc.contributor.authorRen, Yen_HK
dc.date.accessioned2010-09-06T06:14:21Z-
dc.date.available2010-09-06T06:14:21Z-
dc.date.issued2009en_HK
dc.identifier.citationBritish Journal Of Cancer, 2009, v. 101 n. 2, p. 342-349en_HK
dc.identifier.issn0007-0920en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69512-
dc.description.abstractBackground:Gold(III) porphyrin 1a is a new class of anticancer drug, which inhibits cell proliferation of wide range of human cancer cell lines and induces apoptosis in human nasopharyngeal carcinoma cells. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells.Methods:Cell proliferation and apoptosis were determined by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V binding, respectively. Western blot assay was used to detect proteins involved in apoptotic and Akt pathways. In vivo tumour growth was assessed by inoculating tumour cells to nude mice subcutaneously, and gold(III) porphyrin 1a was administrated intravenously.Results:This study assessed the antitumour effect and mechanism of gold(III) porphyrin 1a on neuroblastoma in vitro and in vivo. Gold(III) porphyrin 1a displayed a growth inhibition and induction of apoptosis in neuroblastoma cells effectively in vitro, which was accompanied with release of cytochrome c and Smac/DIABLO and caspases activation. Further studies indicated that gold(III) porphyrin 1a inhibited X-linked inhibitor of apoptosis (XIAP). However, we found that gold(III) porphyrin 1a can induce a survival signal, Akt activation within minutes and could last for at least 24 h. To further confirm association between activation of Akt and the effectiveness of gold(III) porphyrin 1a, neuroblastoma cells were treated with API-2, an Akt-specific inhibitor. API-2 sensitised cells to gold(III) porphyrin 1a-induced apoptosis and growth inhibition.Conclusion:These results suggested that Akt may be considered as a molecular brake that neuroblastoma cells rely on to slow down gold(III) porphyrin 1a-induced apoptosis and antiproliferation. Gold(III) porphyrin 1a is a mitochondrial apoptotic stimulus but also activates Akt, suggesting an involvement of Akt in mediating the effectiveness to growth inhibition and apoptosis by gold(III) porphyrin 1a and that inhibition of Akt can enhance the anticancer activity of gold(III) porphyrin 1a in neuroblastoma. © 2009 Cancer Research UK.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjcen_HK
dc.relation.ispartofBritish Journal of Canceren_HK
dc.subjectAkten_HK
dc.subjectApoptosisen_HK
dc.subjectCaspasesen_HK
dc.subjectGold(III) porphyrin 1aen_HK
dc.subjectNeuroblastomaen_HK
dc.subject.meshApoptosis - drug effects-
dc.subject.meshCaspases - metabolism-
dc.subject.meshMetalloporphyrins - pharmacology-
dc.subject.meshNeuroblastoma - drug therapy - enzymology - pathology-
dc.subject.meshProto-Oncogene Proteins c-akt - antagonists and inhibitors - metabolism-
dc.titleInhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibitionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-0920&volume=101&issue=2&spage=342&epage=349&date=2009&atitle=Inhibition+of+Akt+sensitises+neuroblastoma+cells+to+gold(III)+porphyrin+1a,+a+novel+antitumour+drug+induced+apoptosis+and+growth+inhibitionen_HK
dc.identifier.emailSun, RWY:rwysun@hku.hken_HK
dc.identifier.emailChe, CM:cmche@hku.hken_HK
dc.identifier.emailTam, PK:paultam@hkucc.hku.hken_HK
dc.identifier.authoritySun, RWY=rp00781en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.identifier.authorityTam, PK=rp00060en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1038/sj.bjc.6605147en_HK
dc.identifier.pmid19550420en_HK
dc.identifier.pmcidPMC2720197-
dc.identifier.scopuseid_2-s2.0-67650617274en_HK
dc.identifier.hkuros160684en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67650617274&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume101en_HK
dc.identifier.issue2en_HK
dc.identifier.spage342en_HK
dc.identifier.epage349en_HK
dc.identifier.isiWOS:000268037600020-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLi, W=26643110300en_HK
dc.identifier.scopusauthoridXie, Y=7403958906en_HK
dc.identifier.scopusauthoridSun, RWY=26325835800en_HK
dc.identifier.scopusauthoridLiu, Q=7406296241en_HK
dc.identifier.scopusauthoridYoung, J=27667888000en_HK
dc.identifier.scopusauthoridYu, WY=7403913673en_HK
dc.identifier.scopusauthoridChe, CM=7102442791en_HK
dc.identifier.scopusauthoridTam, PK=7202539421en_HK
dc.identifier.scopusauthoridRen, Y=8109150500en_HK
dc.identifier.citeulike5022533-

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