Please use this identifier to cite or link to this item: https://doi.org/10.1007/s10495-013-0935-2
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dc.titleModulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis
dc.contributor.authorMurphy, A.C
dc.contributor.authorWeyhenmeyer, B
dc.contributor.authorNoonan, J
dc.contributor.authorKilbride, S.M
dc.contributor.authorSchimansky, S
dc.contributor.authorLoh, K.P
dc.contributor.authorKögel, D
dc.contributor.authorLetai, A.G
dc.contributor.authorPrehn, J.H.M
dc.contributor.authorMurphy, B.M
dc.date.accessioned2020-10-27T04:40:38Z
dc.date.available2020-10-27T04:40:38Z
dc.date.issued2014
dc.identifier.citationMurphy, A.C, Weyhenmeyer, B, Noonan, J, Kilbride, S.M, Schimansky, S, Loh, K.P, Kögel, D, Letai, A.G, Prehn, J.H.M, Murphy, B.M (2014). Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis 19 (4) : 629-642. ScholarBank@NUS Repository. https://doi.org/10.1007/s10495-013-0935-2
dc.identifier.issn1360-8185
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/180765
dc.description.abstractGlioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. Treatment failure is associated with intrinsic or acquired apoptosis resistance and the presence of a highly tumourigenic subpopulation of cancer cells called GBM stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising novel therapy for some treatment-resistant tumours but unfortunately GBM can be completely resistant to TRAIL monotherapy. In this study, we identified Mcl-1, an anti-apoptotic Bcl-2 family member, as a critical player involved in determining the sensitivity of GBM to TRAIL-induced apoptosis. Effective targeting of Mcl-1 in TRAIL resistant GBM cells, either by gene silencing technology or by treatment with R-roscovitine, a cyclin-dependent kinase inhibitor that targets Mcl-1, was demonstrated to augment sensitivity to TRAIL, both within GBM cells grown as monolayers and in a 3D tumour model. Finally, we highlight that two separate pathways are activated during the apoptotic death of GBM cells treated with a combination of TRAIL and R-roscovitine, one which leads to caspase-8 and caspase-3 activation and a second pathway, involving a Mcl-1:Noxa axis. In conclusion, our study demonstrates that R-roscovitine in combination with TRAIL presents a promising novel strategy to trigger cell death pathways in glioblastoma. © 2013 The Author(s).
dc.publisherKluwer Academic Publishers
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectactin
dc.subjectcaspase 3
dc.subjectcaspase 8
dc.subjectFLICE inhibitory protein
dc.subjectprocaspase 3
dc.subjectprocaspase 8
dc.subjectprotein Bid
dc.subjectprotein mcl 1
dc.subjectprotein Noxa
dc.subjectroscovitine
dc.subjecttumor necrosis factor related apoptosis inducing ligand
dc.subjectantineoplastic agent
dc.subjectcaspase 3
dc.subjectcaspase 8
dc.subjectMCL1 protein, human
dc.subjectmyeloid leukemia factor 1
dc.subjectPMAIP1 protein, human
dc.subjectprotein bcl 2
dc.subjectpurine derivative
dc.subjecttumor necrosis factor related apoptosis inducing ligand
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcell viability assay
dc.subjectcontrolled study
dc.subjectdisease resistance
dc.subjectdown regulation
dc.subjectenzyme activation
dc.subjectgene silencing
dc.subjectglioblastoma
dc.subjectglioma cell
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman cell culture
dc.subjectneuromodulation
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein targeting
dc.subjectBrain Neoplasms
dc.subjectdrug effects
dc.subjectdrug potentiation
dc.subjectdrug resistance
dc.subjectgenetics
dc.subjectglioblastoma
dc.subjectmetabolism
dc.subjectpathology
dc.subjecttumor cell line
dc.subjectAntineoplastic Agents
dc.subjectApoptosis
dc.subjectBrain Neoplasms
dc.subjectCaspase 3
dc.subjectCaspase 8
dc.subjectCell Line, Tumor
dc.subjectDrug Resistance, Neoplasm
dc.subjectDrug Synergism
dc.subjectEnzyme Activation
dc.subjectGene Silencing
dc.subjectGlioblastoma
dc.subjectHumans
dc.subjectMyeloid Cell Leukemia Sequence 1 Protein
dc.subjectProto-Oncogene Proteins c-bcl-2
dc.subjectPurines
dc.subjectTNF-Related Apoptosis-Inducing Ligand
dc.typeArticle
dc.contributor.departmentDEPT OF CHEMISTRY
dc.description.doi10.1007/s10495-013-0935-2
dc.description.sourcetitleApoptosis
dc.description.volume19
dc.description.issue4
dc.description.page629-642
dc.published.statePublished
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