Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/23225
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dc.contributor.authorButler, L.en
dc.contributor.authorLiapis, V.en
dc.contributor.authorBouralexis, S.en
dc.contributor.authorWelldon, K.en
dc.contributor.authorHay, S.en
dc.contributor.authorThai, L.en
dc.contributor.authorLabrinidis, A.en
dc.contributor.authorTilley, W.en
dc.contributor.authorFindlay, D.en
dc.contributor.authorEvdokiou, A.en
dc.date.issued2006en
dc.identifier.citationInternational Journal of Cancer, 2006; 119(4):944-954en
dc.identifier.issn0020-7136en
dc.identifier.issn1097-0215en
dc.identifier.urihttp://hdl.handle.net/2440/23225-
dc.descriptionThe definitive version may be found at www.wiley.com © 2006 Wiley-Lissen
dc.description.abstractWhile the apoptosis-inducing ligand Apo2L/TRAIL is a promising new agent for the treatment of cancer, the sensitivity of cancer cells for induction of apoptosis by Apo2L/TRAIL varies considerably. Identification of agents that can be used in combination with Apo2L/TRAIL to enhance apoptosis in breast cancer cells would increase the potential utility of this agent as a breast cancer therapeutic. Here, we show that the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can sensitize Apo2L/TRAIL-resistant breast cancer cells to Apo2L/TRAIL-induced apoptosis. Importantly, neither Apo2L/TRAIL alone, nor in combination with SAHA, affected the viability of normal human cells in culture. Apo2L/TRAIL-resistant MDA-MB-231 breast cancer cells, generated by long-term culture in the continuous presence of Apo2L/TRAIL, were resensitized to Apo2L/TRAIL-induced apoptosis by SAHA. The sensitization of these cells by SAHA was accompanied by activation of caspase 8, caspase 9 and caspase 3 and was concomitant with Bid and PARP cleavage. The expression of the proapoptotic protein, Bax, increased significantly with SAHA treatment and high levels of Bax were maintained in the combined treatment with Apo2L/TRAIL. Treatment with SAHA increased cell surface expression of DR5 but not DR4. Interestingly, SAHA treatment also resulted in a significant increase in cell surface expression of DcR1. Taken together, our findings indicate that the use of these 2 agents in combination may be effective for the treatment of breast cancer.en
dc.description.statementofresponsibilityLisa M. Butler, Vasilios Liapis, Stelios Bouralexis, Katie Welldon, Shelley Hay, Le M. Thai, Agatha Labrinidis, Wayne D. Tilley, David M. Findlay, Andreas Evdokiouen
dc.language.isoenen
dc.publisherWiley-lissen
dc.source.urihttp://www3.interscience.wiley.com/cgi-bin/abstract/112511248/ABSTRACTen
dc.subjectApo2L; Apo2L/TRAIL; SAHA; histone deacetylase inhibitors; breast cancer; apoptosisen
dc.titleThe histone deacetylase inhibitor, suberoylanilide hydroxamic acid, overcomes resistance of human breast cancer cells to Apo2L/TRAILen
dc.typeJournal articleen
dc.identifier.rmid0020060940en
dc.identifier.doi10.1002/ijc.21939en
dc.identifier.pubid52611-
pubs.library.collectionOrthopaedics and Trauma publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidButler, L. [0000-0003-2698-3220]en
dc.identifier.orcidTilley, W. [0000-0003-1893-2626]en
dc.identifier.orcidEvdokiou, A. [0000-0001-8321-9806]en
Appears in Collections:Orthopaedics and Trauma publications

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