Search results for "FADD"

showing 10 items of 74 documents

Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasi…

2013

Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused…

Cancer ResearchautophagyCell SurvivalparthenolideFas-Associated Death Domain ProteinImmunologyCASP8 and FADD-Like Apoptosis Regulating ProteinBreast Neoplasmsparthenolide; ROS; NOX; autophagy; breast cancer xenograft.MiceCellular and Molecular Neurosciencechemistry.chemical_compoundDownregulation and upregulationCell Line TumorSettore BIO/10 - BiochimicaAnimalsHumansParthenolidePropidium iodidebreast cancer xenograftMembrane Potential Mitochondrialchemistry.chemical_classificationReactive oxygen speciesNADPH oxidasebiologybreast cancer xenograft.SuperoxideNF-kappa BRNA-Binding ProteinsROSCell BiologyNOXXenograft Model Antitumor AssaysMolecular biologyNuclear Pore Complex ProteinsVascular endothelial growth factorchemistryCell cultureCancer researchbiology.proteinCalciumFemaleOriginal ArticleReactive Oxygen SpeciesSesquiterpenes
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Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells.

2006

AbstractAlthough CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIPL (cFLIPL) and PED/PEA-15, two antiapoptotic proteins whos…

Cancer Researchmedicine.medical_treatmentNF-KAPPA-BOligonucleotidesC-FLIPCASP8 and FADD-Like Apoptosis Regulating ProteinApoptosisSuppressor of Cytokine Signaling ProteinsSIGNALING COMPLEXThyroid cancerTumorCARCINOMA CELLSANDROGEN RECEPTORIntracellular Signaling Peptides and ProteinsInterleukinHASHIMOTOS-THYROIDITISMiddle AgedProtein-Tyrosine KinasesInterleukin-10Up-RegulationMALIGNANT GLIOMA-CELLSInterleukin 10CytokineOncologyAged; Antibodies; Apoptosis; CASP8 and FADD-Like Apoptosis Regulating Protein; Cell Growth Processes; Cell Line Tumor; Humans; Interleukin-10; Interleukin-4; Intracellular Signaling Peptides and Proteins; Janus Kinase 1; Middle Aged; Oligonucleotides Antisense; Phosphoproteins; Protein-Tyrosine Kinases; Repressor Proteins; STAT6 Transcription Factor; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins; Thyroid Neoplasms; Up-Regulation; fas Receptor; Oncology; Cancer Researchmedicine.medical_specialtyANTIAPOPTOTIC PROTEINSCell Growth ProcessesAntibodiesCell LineThyroid carcinomaSuppressor of Cytokine Signaling 1 ProteinSettore MED/04 - PATOLOGIA GENERALEInternal medicineCell Line TumormedicineHumansThyroid Neoplasmsfas ReceptorAntisenseAutocrine signallingInterleukin 4AgedAPOPTOSIS-INDUCING LIGANDbusiness.industryJanus Kinase 1Oligonucleotides Antisensemedicine.diseasePhosphoproteinsRepressor ProteinsEndocrinologyCancer cellCancer researchInterleukin-4businessApoptosis Regulatory ProteinsSTAT6 Transcription FactorCancer research
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The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitizes human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL…

2009

Abstract This paper shows that the histone deacetylase inhibitor SAHA sensitised at sub-toxic doses human hepatocellular carcinoma cells (HepG2, Hep3B and SK-Hep1) to TRAIL-induced apoptosis, while it was ineffective in primary human hepatocytes (PHHs). In particular in HCC cells SAHA increased the expression of death receptor 5 (DR5) and caused a decrement of c-Flip. These two modifications provoked in the presence of TRAIL the rapid production of TRAIL-DISC and the activation of caspase-8. Consequently SAHA/TRAIL combination induced many apoptotic events, such as a cleavage of Bid into tBid, dissipation of mitochondrial membrane potential, activation of caspase-3 with the consequent cleav…

Death Domain Receptor Signaling Adaptor ProteinsCancer Researchmedicine.medical_specialtyProgrammed cell deathCarcinoma Hepatocellularmedicine.drug_classmedicine.medical_treatmentBlotting WesternCASP8 and FADD-Like Apoptosis Regulating ProteinDown-RegulationAntineoplastic AgentsApoptosisBiologyHydroxamic AcidsHDACI TRAIL apoptosisInternal medicineSettore BIO/10 - BiochimicamedicineHumansProtein kinase BVorinostatLiver NeoplasmsHistone deacetylase inhibitorNF-kappa Bmedicine.diseaseReceptors TNF-Related Apoptosis-Inducing LigandCytokineEndocrinologyOncologyDrug Resistance NeoplasmApoptosisHepatocellular carcinomaCancer researchTumor necrosis factor alphaSignal transductionProto-Oncogene Proteins c-akt
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CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells

2004

We investigated the membrane localization of CD95 in type I and type II cells, which differ in their ability to recruit and activate caspase-8. We found that CD95 was preferentially located in lipid rafts of type I cells, while it was present both in raft and non-raft plasma membrane sub-domains of type II cells. After stimulation, CD95 located in phospholipid-rich plasma membrane was recruited to lipid rafts in both types of cells. Similarly, CD95 cross-linking resulted in caspase-independent translocation of FADD/MORT1 and caspase-8 to the lipid rafts, which was prevented by a death domain-defective receptor. CD95 internalization was then rapid in type I and delayed in type II cells and s…

Death Domain Receptor Signaling Adaptor ProteinsEndosomeT-Lymphocytesmedia_common.quotation_subjectImmunologyApoptosisReceptors Tumor Necrosis FactorCell LineMembrane MicrodomainsSettore MED/04 - PATOLOGIA GENERALECell Line TumorReceptorsHumansImmunology and Allergyfas ReceptorFADDInternalizationLipid raftLipid raftsDeath domainmedia_commonTumorbiologyVesicleFas receptorEndocytosisCell biologyProtein TransportCholesterolCD95 death-inducing signaling complexCaspasesCD95biology.proteinlipids (amino acids peptides and proteins)biological phenomena cell phenomena and immunityCaspase-8Tumor Necrosis FactorCaspase-8; CD95; Lipid rafts; Apoptosis; Caspases; Cell Line Tumor; Cholesterol; Death Domain Receptor Signaling Adaptor Proteins; Humans; Membrane Microdomains; Protein Binding; Protein Transport; Receptors Tumor Necrosis Factor; T-Lymphocytes; fas Receptor; Endocytosis; Signal Transduction; Immunology and Allergy; ImmunologyProtein BindingSignal TransductionEuropean Journal of Immunology
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Three-body approach to proton-hydrogen charge exchange and elastic scattering

1999

The impact-parameter Faddeev approach to atomic three-body collisions which has been developed for, and successfully applied to, ion-atom scattering processes, has now been developed further by including, instead of the Coulomb potentials, the full two-particle off-shell Coulomb {ital T} matrices in all {open_quotes}triangle{close_quotes} contributions to the effective potentials. Results of calculations of proton-hydrogen collisions with only the ground states of the hydrogen retained in both the direct and the rearrangement channels are presented. Total and differential electron transfer, as well as differential elastic scattering cross sections, are obtained simultaneously in very good a…

Elastic scatteringPhysicsFaddeev equationsRange (particle radiation)ProtonScatteringTransfer-matrix method (optics)CoulombAtomic physicsThree-body problemAtomic and Molecular Physics and Optics
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Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination.

2010

Abstract Apoptosis of oligodendrocytes (ODCs), the myelin-producing glial cells in the CNS, plays a central role in demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To investigate the mechanism behind ODC apoptosis in EAE, we made use of conditional knockout mice lacking the adaptor protein FADD specifically in ODCs (FADDODC-KO). FADD mediates apoptosis by coupling death receptors with downstream caspase activation. In line with this, ODCs from FADDODC-KO mice were completely resistant to death receptor-induced apoptosis in vitro. In the EAE model, FADDODC-KO mice followed an ameliorated clinical di…

Encephalomyelitis Autoimmune ExperimentalMultiple Sclerosisgenetic structuresEncephalomyelitisFas-Associated Death Domain ProteinImmunologyApoptosisurologic and male genital diseasesMiceConditional gene knockoutDemyelinating diseasemedicineImmunology and AllergyAnimalsFADDLymphocytesMyelin SheathDeath domainInflammationMice KnockoutbiologyMultiple sclerosisMacrophagesfungiExperimental autoimmune encephalomyelitismedicine.diseaseOligodendrocyteOligodendrogliamedicine.anatomical_structureGene Expression RegulationSpinal CordCancer researchbiology.proteinbiological phenomena cell phenomena and immunityGene DeletionJournal of immunology (Baltimore, Md. : 1950)
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p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation.

2003

The mechanism of p53-dependent apoptosis is still only partly defined. Using early-passage embryonic fibroblasts (MEF) from wild-type (wt), p53(-/-) and bax(-/-) mice, we observe a p53-dependent translocation of Bax to the mitochondria and a release of mitochondrial Cytochrome c during stress-induced apoptosis. These events proceed independent of zVAD-inhibitable caspase activation, are not prevented by dominant negative FADD (DN-FADD), but are negatively regulated by Mdm-2. Bcl-x(L) expression prevents the release of mitochondrial Cytochrome c and apoptosis, but not Bax translocation. At a single-cell level, enforced expression of p53 is sufficient to induce Bax translocation and Cytochrom…

Fas-Associated Death Domain ProteinDown-RegulationChromosomal translocationApoptosisCytochrome c GroupMitochondrionMiceBcl-2-associated X proteinFetusDownregulation and upregulationProto-Oncogene ProteinsAnimalsFADDEnzyme InhibitorsMolecular BiologyCells CulturedAdaptor Proteins Signal Transducingbcl-2-Associated X ProteinMice KnockoutbiologyOncogeneChemistryCytochrome cCell BiologyFibroblastsMolecular biologyCell biologyMitochondriaProtein TransportGene Expression RegulationProto-Oncogene Proteins c-bcl-2ApoptosisCaspasesbiology.proteinTumor Suppressor Protein p53Carrier ProteinsCell death and differentiation
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Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an anti-apoptotic viral gene

2008

ABSTRACT Genes that inhibit apoptosis have been described for many DNA viruses. Herpesviruses often contain even more than one gene to control cell death. Apoptosis inhibition by viral genes is postulated to contribute to viral fitness, although a formal proof is pending. To address this question, we studied the mouse cytomegalovirus (MCMV) protein M36, which binds to caspase-8 and blocks death receptor-induced apoptosis. The growth of MCMV recombinants lacking M36 (ΔM36) was attenuated in vitro and in vivo. In vitro, caspase inhibition by zVAD-fmk blocked apoptosis in ΔM36-infected macrophages and rescued the growth of the mutant. In vivo, ΔM36 infection foci in liver tissue contained sign…

Genes ViralFas-Associated Death Domain ProteinvirusesImmunologyMutantCytomegalovirusCellular Response to InfectionApoptosisMicrobiologyVirusCell LineMiceIn vivoVirologyAnimalsFADDCaspaseDNA PrimersGenes DominantMice Inbred BALB CBase Sequencebiologyanti-apoptotic viral geneBIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.MCMV; FADD; anti-apoptotic viral geneFlow CytometryMolecular biologyMice Inbred C57BLViral replicationApoptosisVirion assemblyInsect ScienceFADDbiology.proteinBIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.MCMV
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Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

2014

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for stud…

Genotyping TechniquesResearch Support U.S. Gov't P.H.S.CASP8 and FADD-Like Apoptosis Regulating ProteinGenome-wide association studyP.H.S.Medical and Health SciencesBreast and Ovarian Cancer Susceptibility (BOCS) StudyMedizinische FakultätGenetics(clinical)Non-U.S. Gov'tGenetics (clinical)GeneticsGenetics & HeredityvariantsCaspase 8Research Support Non-U.S. Gov'tAssociation Studies ArticlesGeneral MedicineBiological Sciencesddc:Chromosomes Human Pair 2kConFab InvestigatorsFemaleGENICA NetworkAustralian Ovarian Cancer Study GroupEuropean Continental Ancestry GroupNon-P.H.S.Single-nucleotide polymorphismBreast Neoplasms-BiologyResearch SupportPolymorphism Single NucleotideWhite PeopleN.I.H.Breast cancerResearch Support N.I.H. ExtramuralSDG 3 - Good Health and Well-beingmedicineGeneticsJournal ArticleHumansGenetic Predisposition to Diseaseddc:610geneGenotyping TechniquesGenotypingMolecular BiologyGenetic associationdiseaseExtramuralProteinsOdds ratiomedicine.diseasesusceptibility lociMinor allele frequencyCase-Control Studiesgenome-wide associationenhancersU.S. Gov'tcasp8Research Support U.S. Gov't Non-P.H.S.Genome-Wide Association Study
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cFLIPL Inhibits Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated NF-κB Activation at the Death-inducing Signaling Complex in Human Ke…

2004

Human keratinocytes undergo apoptosis following treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via surface-expressed TRAIL receptors 1 and 2. In addition, TRAIL triggers nonapoptotic signaling pathways including activation of the transcription factor NF-kappaB, in particular when TRAIL-induced apoptosis is blocked. The intracellular protein cFLIP(L) interferes with TRAIL-induced apoptosis at the death-inducing signaling complex (DISC) in many cell types. To study the role of cFLIP(L) in TRAIL signaling, we established stable HaCaT keratinocyte cell lines expressing varying levels of cFLIP(L). Functional analysis revealed that relative cFLIP(L) levels correlat…

KeratinocytesCytoplasmReceptor complexCell SurvivalCASP8 and FADD-Like Apoptosis Regulating ProteinApoptosisCell SeparationBiologyCaspase 8Sensitivity and SpecificityBiochemistryProinflammatory cytokineTNF-Related Apoptosis-Inducing LigandRibonucleasesCell Line TumorHumansEnzyme InhibitorsMolecular BiologyTranscription factorSkinInflammationCaspase 8Membrane GlycoproteinsTumor Necrosis Factor-alphaIntracellular Signaling Peptides and ProteinsNF-kappa BCell BiologyFlow CytometryRecombinant ProteinsCell biologyRetroviridaeApoptosisCaspasesDeath-inducing signaling complexRNATumor necrosis factor alphaSignal transductionApoptosis Regulatory ProteinsPropidiumProtein BindingSignal TransductionJournal of Biological Chemistry
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