2008
Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation
Zhang G, Park MA, Mitchell C, Hamed H, Rahmani M, Martin AP, Curiel DT, Yacoub A, Graf M, Lee R, Roberts JD, Fisher PB, Grant S, Dent P. Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation. Clinical Cancer Research 2008, 14: 5385-5399. PMID: 18765530, PMCID: PMC2561272, DOI: 10.1158/1078-0432.ccr-08-0469.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma cellsLong-term colony formation assaysCaspase-8C-FLIPExtracellular signal-regulated kinase 1/2Full-length BidSignal-regulated kinase 1/2Activation of BaxKnockdown of CD95Multiple antiapoptotic proteinsExpression of BimColony formation assaysAdenocarcinoma cellsVorinostat treatmentCD95 activationKill Tumor CellsProapoptotic signalsProtease pathwayKinase 1/2Caspase-9Cathepsin proteasesAntiapoptotic proteinsBcl-xLFADD expressionMcl-1
2007
Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells
Mitchell C, Park MA, Zhang G, Yacoub A, Curiel DT, Fisher PB, Roberts JD, Grant S, Dent P. Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells. Molecular Cancer Therapeutics 2007, 6: 3101-3112. PMID: 18065490, DOI: 10.1158/1535-7163.mct-07-0561.Peer-Reviewed Original ResearchConceptsBcl-xLC-FLIPBreast cancer cellsMitogen-activated protein/ERK kinase 1X-chromosome-linked inhibitorCancer cellsExtracellular signal-regulated kinase 1/2Apoptosis protein levelsSignal-regulated kinase 1/2ERK kinase 1CDK inhibitor roscovitineIntrinsic apoptosis pathwayHistone deacetylase inhibitor suberoylanilide hydroxamic acidForm of AktProtease-dependent pathwayInhibition of AktTreatment of cellsBak functionBcl-xL expressionCell killingCyclin-dependent kinase inhibitor flavopiridolInhibitor suberoylanilide hydroxamic acidKinase inhibitor flavopiridolERK1/2 functionAkt activity