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dc.contributor.authorBuontempo, F.en_US
dc.contributor.authorErsahin, T.en_US
dc.contributor.authorMissiroli, S.en_US
dc.contributor.authorSenturk, S.en_US
dc.contributor.authorEtro, D.en_US
dc.contributor.authorOzturk, M.en_US
dc.contributor.authorCapitani, S.en_US
dc.contributor.authorCetin Atalay, R.en_US
dc.contributor.authorNeri, M. L.en_US
dc.date.accessioned2016-02-08T09:49:59Z
dc.date.available2016-02-08T09:49:59Z
dc.date.issued2011en_US
dc.identifier.issn0167-6997
dc.identifier.urihttp://hdl.handle.net/11693/21701
dc.description.abstractThe serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lines, and tested cytotoxic effects of Akt pathway inhibitors LY294002, Wortmannin and Inhibitor VIII. In Mahlavu human hepatoma cells Akt was constitutively activated, as demonstrated by its Ser473 phosphorylation, downstream hyperphosphorylation of BAD on Ser136, and by a specific cell-free kinase assay. In contrast, Huh7 and HepG2 did not show hyperactivation when tested by the same criteria. Akt enzyme hyperactivation in Mahlavu was associated with a loss of PTEN protein expression. Akt signaling was inhibited by the upstream kinase inhibitors, LY294002, Wortmannin, as well as by the specific Akt Inhibitor VIII in all three hepatoma cell lines. Cytotoxicity assays with Akt inhibitors in the same cell lines indicated that they were all sensitive, but with different IC50 values as assayed by RT-CES. We also demonstrated that the cytotoxic effect was through apoptotic cell death. Our findings provide evidence for its constitutive activation in one HCC cell line, and that HCC cell lines, independent of their Akt activation status respond to Akt inhibitors by apoptotic cell death. Thus, Akt inhibition may be considered as an attractive therapeutic intervention in liver cancer. © Springer Science+Business Media, LLC 2010.en_US
dc.language.isoEnglishen_US
dc.source.titleInvestigational New Drugsen_US
dc.relation.isversionofhttp://dx.doi.org/10.1007/s10637-010-9486-3en_US
dc.subjectAkten_US
dc.subjectHCCen_US
dc.subjectInhibitor VIIIen_US
dc.subjectLY294002en_US
dc.subjectPI3Ken_US
dc.subjectPTENen_US
dc.subjectRTCESen_US
dc.subjectWortmanninen_US
dc.titleInhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation statusen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage1303en_US
dc.citation.epage1313en_US
dc.citation.volumeNumber29en_US
dc.citation.issueNumber6en_US
dc.identifier.doi10.1007/s10637-010-9486-3en_US
dc.publisherSpringeren_US


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