2018
Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells
Šalovská B, Janečková H, Fabrik I, Karlíková R, Čecháková L, Ondrej M, Link M, Friedecký D, Tichý A. Radio-sensitizing effects of VE-821 and beyond: Distinct phosphoproteomic and metabolomic changes after ATR inhibition in irradiated MOLT-4 cells. PLOS ONE 2018, 13: e0199349. PMID: 30001349, PMCID: PMC6042708, DOI: 10.1371/journal.pone.0199349.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAtaxia Telangiectasia Mutated ProteinsBinding SitesBiomarkersCell Cycle CheckpointsCell Line, TumorComputational BiologyGamma RaysGene OntologyHumansMetabolomeMetabolomicsPhosphoproteinsPhosphorylationProtein BindingProtein Kinase InhibitorsProteomeProteomicsPyrazinesRadiation ToleranceRadiation-Sensitizing AgentsSignal TransductionSulfonesTOR Serine-Threonine KinasesConceptsVE-821MOLT-4 cellsCellular metabolismOncogene-induced replication stressATR inhibitionATM-deficient cellsDNA damage responseATR/Chk1 pathwayCell biology techniquesDownregulation of mTORAnti-cancer strategyCurrent anti-cancer strategiesReplication stressPhosphorylation sitesDamage responseIrradiation-induced oxidative stressQuantitative proteomicsDNA repairChk1 pathwayCellular eventsBiology techniquesSpecific inhibitorMain regulatorTumor-specific abnormalitiesMTOR inhibition
2014
Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis
Šalovská B, Fabrik I, Ďurišová K, Link M, Vávrová J, Řezáčová M, Tichý A. Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis. International Journal Of Molecular Sciences 2014, 15: 12007-12026. PMID: 25003641, PMCID: PMC4139827, DOI: 10.3390/ijms150712007.Peer-Reviewed Original ResearchMeSH KeywordsAtaxia Telangiectasia Mutated ProteinsCell Line, TumorGamma RaysHumansPhosphorylationProtein Kinase InhibitorsProteomePyrazinesRadiation-Sensitizing AgentsSulfonesConceptsDNA-dependent protein kinaseVE-821HL-60 cellsNano-liquid chromatography-tandem mass spectrometry analysisCell cycleSequence motif analysisDNA damage responseRadiation-induced double-strand breaksATR kinase inhibitorsDNA damage repairDNA damaging agentsHuman leukemic HL-60 cellsDouble-strand breaksSpecific ATR inhibitorActivity of kinasesInhibitor VE-821Leukemic HL-60 cellsCell cycle arrestQuantitative phosphoproteomicsATR kinaseMotif analysisPhosphorylation sitesCellular processesDamage responsePhosphoproteomic analysis
2013
Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441
Tichy A, Durisova K, Salovska B, Pejchal J, Zarybnicka L, Vavrova J, Dye N, Sinkorova Z. Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441. Radiation And Environmental Biophysics 2013, 53: 83-92. PMID: 24100951, DOI: 10.1007/s00411-013-0494-5.Peer-Reviewed Original ResearchConceptsDNA-dependent protein kinasePhosphorylation of H2A.XMOLT-4 cellsDNA-dependent protein kinase inhibitorDNA repair signalingProtein kinase inhibitorsAnti-apoptotic Mcl-1Cleavage of PARPHistone H2A.X.Cdc25A phosphataseProtein kinaseRepair signalingMolecular mechanismsNU7441Mcl-1Detection of IRDNA damageSpecific inhibitorPhosphorylationDetection of proteinsH2A.XSubsequent inductionKinase inhibitorsWestern blottingApoptosisDNA-dependent protein kinase and its inhibition in support of radiotherapy
Novotná E, Tichý A, Pejchal J, Lukášová E, Šalovská B, Vávrová J. DNA-dependent protein kinase and its inhibition in support of radiotherapy. International Journal Of Radiation Biology 2013, 89: 416-423. PMID: 23362996, DOI: 10.3109/09553002.2013.767993.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA RepairDNA-Activated Protein KinaseHumansNeoplasmsRadiation-Sensitizing AgentsRadiotherapyConceptsDNA-dependent protein kinaseRadiation-induced double strand break repairProtein kinaseDouble-strand break repairDNA repair proteinsDNA-PK inhibitionDNA-PK inhibitorKey DNA repair enzymeDNA repair enzymeBreak repairRepair proteinsPersonalized anti-cancer therapyRepair enzymesMolecular approachesMolecular mechanismsAnti-cancer therapyRecent discoveryCancer cellsKinaseRecent knowledgeRNASmall peptidesPivotal roleRecent studiesCancer therapy
2012
Radio-Sensitization of Human Leukaemic MOLT-4 Cells by DNA-Dependent Protein Kinase Inhibitor, NU7026
Tichý A, Novotná E, Ďurišová K, Šalovská B, Sedlaříková R, Pejchal J, Zárybnická L, Vávrová J, Šinkorová Z, Řezáčová M. Radio-Sensitization of Human Leukaemic MOLT-4 Cells by DNA-Dependent Protein Kinase Inhibitor, NU7026. Acta Medica 2012, 55: 66-73. PMID: 23101268, DOI: 10.14712/18059694.2015.57.Peer-Reviewed Original ResearchConceptsMOLT-4 cellsDNA repairDNA-dependent protein kinase inhibitorDNA-dependent protein kinaseDNA damage responsePost-translational modificationsCheckpoint kinase 2Protein kinase inhibitorsG2 phase arrestInduction of apoptosisATM kinaseDamage responseProtein kinaseKinase 2Cell cycle analysisNU7026Specific inhibitorCellular mechanismsPronounced apoptosisApoptosisKinase inhibitorsAmount of cellsCellsCycle analysisInhibitors