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-1Transient exposure of carcinoma cells to RAS/MEK inhibitors and UCN-01 causes cell death in vitro and in vivo
Hamed H, Hawkins W, Mitchell C, Gilfor D, Zhang G, Pei XY, Dai Y, Hagan MP, Roberts JD, Yacoub A, Grant S, Dent P. Transient exposure of carcinoma cells to RAS/MEK inhibitors and UCN-01 causes cell death in vitro and in vivo. Molecular Cancer Therapeutics 2008, 7: 616-629. PMID: 18347148, DOI: 10.1158/1535-7163.mct-07-2376.Peer-Reviewed Original ResearchConceptsMammary carcinoma cellsCarcinoma cellsMammary tumorsTumor growthUCN-01Tumor cellsMEK1/2 inhibitor PD184352MEK1/2 inhibitorMammary tumor growthMean tumor volumeTransient exposureTumor growth rateHuman mammary carcinoma cellsColony formation assaysExpression of BaxColony formation studiesMEK1/2 inhibitor treatmentFarnesyl transferase inhibitorsCell tumorsDrug exposureDrug treatmentTumor volumeAthymic miceDrug AdministrationInhibitor treatment
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
2005
Transient exposure of mammary tumors to PD184352 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor re-growth
Hawkins W, Mitchell C, McKinstry R, Gilfor D, Starkey J, Dai Y, Dawson K, Ramakrishnan V, Roberts JD, Yacoub A, Grant S, Dent P. Transient exposure of mammary tumors to PD184352 and UCN-01 causes tumor cell death in vivo and prolonged suppression of tumor re-growth. Cancer Biology & Therapy 2005, 4: 1275-1284. PMID: 16319524, DOI: 10.4161/cbt.4.11.2286.Peer-Reviewed Original ResearchConceptsTumor cell deathTumor growthMDA-MB-231Drug exposureTumor volumeUCN-01Cell deathTumor cellsMCF7 tumor growthMDA-MB-231 tumorsMEK1/2 inhibitorMean tumor volumeMammary tumor growthTransient exposureTumor growth rateHuman mammary carcinoma cellsK-RAS expressionCombination index valuesMammary carcinoma cellsColony formation assaysPhosphorylation of ERK1/2Colony formation studiesEstrogen dependencyMammary tumorsProlonged suppression