2007
Proteomic Analysis of the Resistance to Aplidin in Human Cancer Cells
González-Santiago L, Alfonso P, Suárez Y, Núñez A, García-Fernández LF, Alvarez E, Muñoz A, Casal JI. Proteomic Analysis of the Resistance to Aplidin in Human Cancer Cells. Journal Of Proteome Research 2007, 6: 1286-1294. PMID: 17338558, DOI: 10.1021/pr060430+.Peer-Reviewed Original ResearchConceptsProtein disulfide isomeraseRole of PDINumber of proteinsRab geranylgeranyltransferaseInduction of apoptosisHuman cancer cellsDisulfide isomeraseProteomic approachMembrane proteinsProteomic analysisMALDI-TOF mass spectrometryApoptosis pathwayDatabase interrogationHeLa cellsCyclophilin AProteinCancer cellsAplidinApoptosisCystathionine gamma lyaseCellsMass spectrometryGeranylgeranyltransferaseEzrinIsomerase
2006
Plitidepsin Cellular Binding and Rac1/JNK Pathway Activation Depend on Membrane Cholesterol Content
Suárez Y, González-Santiago L, Zarich N, Dávalos A, Aranda JF, Alonso MA, Lasunción MA, Rojas JM, Muñoz A. Plitidepsin Cellular Binding and Rac1/JNK Pathway Activation Depend on Membrane Cholesterol Content. Molecular Pharmacology 2006, 70: 1654-1663. PMID: 16928956, DOI: 10.1124/mol.106.025569.Peer-Reviewed Original ResearchConceptsJun N-terminal kinaseMembrane cholesterol contentRac1-JNK pathwayHeLa cellsWild-type HeLa cellsMembrane-bound Rac1Plasma membrane cholesterolRac1 small GTPaseN-terminal kinaseMKP-1 phosphataseJNK pathway activationCellular bindingMDA-MB-231 breast cancer cellsInduction of apoptosisSmall GTPaseMarine cyclic depsipeptidePlasma membraneJNK activationRac1 activationMembrane cholesterolCell deathSubcellular fractioningBreast cancer cellsSustained activationRac1Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation
González-Santiago L, Suárez Y, Zarich N, Muñoz-Alonso M, Cuadrado A, Martínez T, Goya L, Iradi A, Sáez-Tormo G, Maier J, Moorthy A, Cato A, Rojas J, Muñoz A. Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation. Cell Death & Differentiation 2006, 13: 1968-1981. PMID: 16543941, DOI: 10.1038/sj.cdd.4401898.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCalciumCell Cycle ProteinsCopperDepsipeptidesDown-RegulationDual Specificity Phosphatase 1Enzyme ActivationGlutathione DisulfideGlutathione PeroxidaseGlutathione ReductaseHeLa CellsHomeostasisHumansImmediate-Early ProteinsJNK Mitogen-Activated Protein KinasesMembrane PotentialsMiceMitochondrial MembranesOxidative StressPeptides, CyclicPhosphoprotein PhosphatasesProtein Phosphatase 1Protein Tyrosine PhosphatasesRac1 GTP-Binding ProteinReactive Oxygen SpeciesConceptsJun N-terminal kinaseJNK activationRac1 activationGlutathione homeostasisRac1 small GTPaseJNK-dependent apoptosisRac1 GTPase activationMitochondrial membrane potentialN-terminal kinaseMKP-1 phosphataseSmall GTPaseGTPase activationReactive oxygen speciesHuman breast cancer cellsGSSG/GSH ratioCell deathBreast cancer cellsRapid activationExogenous GSHRNA duplexesSustained activationGSH synthesisSpecific Rac1 inhibitorAplidinDownregulation of Rac1
2004
JNK activation is critical for Aplidin™-induced apoptosis
Cuadrado A, González L, Suárez Y, Martínez T, Muñoz A. JNK activation is critical for Aplidin™-induced apoptosis. Oncogene 2004, 23: 4673-4680. PMID: 15122339, DOI: 10.1038/sj.onc.1207636.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsApoptosisBlotting, WesternBreast NeoplasmsCell DivisionCell Line, TumorCell SurvivalDepsipeptidesEnzyme ActivationFemaleFibroblastsHumansMitogen-Activated Protein KinasesNF-kappa BPeptides, CyclicPhosphorylationPrecipitin TestsProto-Oncogene Proteins c-junTranscription Factor AP-1
2002
AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*
Cuadrado A, Garcı́a-Fernández L, González L, Suárez Y, Losada A, Alcaide V, Martı́nez T, Fernández-Sousa J, Sánchez-Puelles J, Muñoz A. AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK*. Journal Of Biological Chemistry 2002, 278: 241-250. PMID: 12414812, DOI: 10.1074/jbc.m201010200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCell DivisionCell SurvivalCells, CulturedDepsipeptidesEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFemaleFibroblastsFlow CytometryGlutathioneHumansJNK Mitogen-Activated Protein KinasesKidney NeoplasmsMiceMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPeptides, CyclicPhosphorylationProto-Oncogene Proteins pp60(c-src)Receptors, Platelet-Derived Growth FactorTumor Cells, CulturedConceptsEpidermal growth factor receptorP38 MAPK activationP38 MAPKNon-receptor protein tyrosine kinase SrcGrowth factor receptorMAPK activationProtein tyrosine kinase SrcStress response programSustained activationFactor receptorCancer cellsMDA-MB-231 breast cancer cellsHuman cancer cellsBenzyloxycarbonyl-VADKinase SrcHuman MDA-MB-231 breast cancer cellsMDA-MB-231 cellsMolecular basisKinase JNKPretreatment of cellsMouse embryosEGFR activationFluoromethyl ketoneGrowth arrestHuman renal cancer