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 ResearchMeSH KeywordsCell MembraneCholesterolDepsipeptidesDrug Resistance, NeoplasmEnzyme ActivationHeLa CellsHumansJNK Mitogen-Activated Protein KinasesPeptides, CyclicProtein TransportRac1 GTP-Binding ProteinTumor Cells, CulturedConceptsJun 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
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