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Article: FTY720 induces apoptosis of human hepatoma cell lines through cell lines through P13-K-mediated Akt dephosphorylation

TitleFTY720 induces apoptosis of human hepatoma cell lines through cell lines through P13-K-mediated Akt dephosphorylation
Authors
Issue Date2004
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2004, v. 25 n. 12, p. 2397-2405 How to Cite?
AbstractOur aim was to study the anticancer effect of the novel immunomodulator FTY720 in vitro and in vivo by investigation of cell cycle entry, cell cycle regulation, cell survival and apoptosis pathways. Three hepatoma cell lines with different p53 statuses (HepG2, Huh-7 and Hep3B) and one non-tumorigenic immortalized liver cell line (MIHA) were used for an in vitro study. The in vivo effects of FTY720 were evaluated in a nude mouse tumor model. Cell cycle distribution and cell cycle regulator proteins p27Kip1 and cyclin D1, together with the PI3-K/Akt pathway, mitogen-activated protein kinases and cleaved caspase-3 and caspase-9, were evaluated. FTY720 selectively induced cell apoptosis in hepatoma cell lines with overexpression of cleaved caspase-3 and caspase-9, but the same phenomena were not found in MIHA cells. FTY720 induced Akt dephosphorylation at Ser473 mediated by phosphoinositide 3-kinase (PI3-K) inhibition. Dephosphorylation led to down-regulation of p42/p44 and dephosphorylation of Forkhead transcription factor and GSK-3β and, subsequently, up-regulation of p27Kip1 and down-regulation of cyclin D1. In our in vivo model FTY720 induced apoptosis of tumor cells by down-regulation of the Akt pathway. FTY720 suppressed tumor growth without notable side-effects in normal liver. In conclusion, FTY720 is a novel anticancer agent that induces apoptosis of hepatoma cell lines both in vitro and in vivo through PI3-K-mediated Akt dephosphorylation in a p53-independent manner. © Oxford University Press 2004; all rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/148374
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, TKen_HK
dc.contributor.authorMan, Ken_HK
dc.contributor.authorHo, JWen_HK
dc.contributor.authorSun, CKen_HK
dc.contributor.authorNg, KTen_HK
dc.contributor.authorWang, XHen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorNg, IOen_HK
dc.contributor.authorXu, Ren_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2012-05-29T06:12:34Z-
dc.date.available2012-05-29T06:12:34Z-
dc.date.issued2004en_HK
dc.identifier.citationCarcinogenesis, 2004, v. 25 n. 12, p. 2397-2405en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148374-
dc.description.abstractOur aim was to study the anticancer effect of the novel immunomodulator FTY720 in vitro and in vivo by investigation of cell cycle entry, cell cycle regulation, cell survival and apoptosis pathways. Three hepatoma cell lines with different p53 statuses (HepG2, Huh-7 and Hep3B) and one non-tumorigenic immortalized liver cell line (MIHA) were used for an in vitro study. The in vivo effects of FTY720 were evaluated in a nude mouse tumor model. Cell cycle distribution and cell cycle regulator proteins p27Kip1 and cyclin D1, together with the PI3-K/Akt pathway, mitogen-activated protein kinases and cleaved caspase-3 and caspase-9, were evaluated. FTY720 selectively induced cell apoptosis in hepatoma cell lines with overexpression of cleaved caspase-3 and caspase-9, but the same phenomena were not found in MIHA cells. FTY720 induced Akt dephosphorylation at Ser473 mediated by phosphoinositide 3-kinase (PI3-K) inhibition. Dephosphorylation led to down-regulation of p42/p44 and dephosphorylation of Forkhead transcription factor and GSK-3β and, subsequently, up-regulation of p27Kip1 and down-regulation of cyclin D1. In our in vivo model FTY720 induced apoptosis of tumor cells by down-regulation of the Akt pathway. FTY720 suppressed tumor growth without notable side-effects in normal liver. In conclusion, FTY720 is a novel anticancer agent that induces apoptosis of hepatoma cell lines both in vitro and in vivo through PI3-K-mediated Akt dephosphorylation in a p53-independent manner. © Oxford University Press 2004; all rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCarcinoma, Hepatocellular - Metabolism - Pathologyen_US
dc.subject.meshCell Cycle Proteins - Metabolismen_US
dc.subject.meshCyclin D1 - Metabolismen_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P27en_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshG1 Phase - Drug Effectsen_US
dc.subject.meshGlycogen Synthase Kinase 3 - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunosuppressive Agents - Pharmacologyen_US
dc.subject.meshLiver Neoplasms - Metabolism - Pathologyen_US
dc.subject.meshMitogen-Activated Protein Kinase 1 - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshMitogen-Activated Protein Kinase 3 - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshPhosphatidylinositol 3-Kinases - Metabolismen_US
dc.subject.meshPhosphorylation - Drug Effectsen_US
dc.subject.meshPropylene Glycols - Pharmacologyen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins C-Akten_US
dc.subject.meshSphingosine - Analogs & Derivativesen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshTumor Suppressor Protein P53 - Metabolismen_US
dc.subject.meshTumor Suppressor Proteins - Metabolismen_US
dc.titleFTY720 induces apoptosis of human hepatoma cell lines through cell lines through P13-K-mediated Akt dephosphorylationen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, TK: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailMan, K: kwanman@hku.hken_HK
dc.identifier.emailNg, KT: ledodes@hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.emailNg, IO: iolng@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityMan, K=rp00417en_HK
dc.identifier.authorityNg, KT=rp01720en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.authorityNg, IO=rp00335en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/carcin/bgh250en_HK
dc.identifier.pmid15297371-
dc.identifier.scopuseid_2-s2.0-10344231428en_HK
dc.identifier.hkuros97062-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-10344231428&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2397en_HK
dc.identifier.epage2405en_HK
dc.identifier.isiWOS:000225531900014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridMan, K=7101754072en_HK
dc.identifier.scopusauthoridHo, JW=7402649982en_HK
dc.identifier.scopusauthoridSun, CK=7404248685en_HK
dc.identifier.scopusauthoridNg, KT=7403178513en_HK
dc.identifier.scopusauthoridWang, XH=7501854829en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK
dc.identifier.scopusauthoridNg, IO=7102753722en_HK
dc.identifier.scopusauthoridXu, R=8652263200en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.citeulike60428-

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