Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3a.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2b.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2a.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3b.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1b.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1a.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2a.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1b.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1a.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3a.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2b.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3b.mzid.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1a.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1a.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1b.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3b.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2a.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1b.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2b.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2b.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2a.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3a.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3b.pride.mgf.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3a.mgfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2a.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1b.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_1a.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3b.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_3a.pride.mztab.gzftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD004793/SW480_ne_KP1339_2b.pride.mztab.gzprimaryOK200Christopher GernerSw-480 CellColon Epithelial CellColonSW480, kindly provided by Michael Jakupec (Department of Inorganic Chemistry, University of Vienna, Austria), were cultured in EMEM (Sigma-Aldrich, USA) supplemented with 10% FCS, 100U/ml penicillin/streptomycin, 0.1mM non-essential amino acids and 1mM sodium pyruvate at 37°C and 5% CO2. Cells were treated with 80µM KP1339. Experiments were conducted for 24 hours in T25 flasks in triplicates with on average 107 cells per flasks. With the combination of an isotonic lysis buffer containing protease inhibitors and shear stress cytoplasmic proteins were released and after centrifugation (2300xg, 5min, 4°C) precipitated with ice-cold ethanol at -20°C over night. The nuclei were incubated first with a solution containing 500mM NaCl and then with a NP-40 buffer supplemented with protease inhibitors. The remaining cell material was separated by centrifugation; nuclear proteins were again precipitated with ice-cold ethanol at -20°C over night. Precipitated proteins were dissolved in sample buffer (7.5M urea, 1.5M thiourea, 4% CHAPS, 0.05% SDS, 100mM dithiothreitol (DTT)) and a Bradford assay (Bio-Rad-Laboratories, Germany) was employed to determine protein concentrations. In solution digestions were performed with 25µg of protein. The samples were pre-concentrated on 10kDa filters (Pall Austria Filter GmbH), reduced with DTT (56°C, 30 min) and carbamidomethylated with iodacetamide (45 min in the dark). To receive peptides, samples were digested with a trypsin/lys-c mixture (Promega, Germany) for 18h at 37°C. Eluates were dried and stored at -20°C until analysis. For analysis a nanoLC-system (Dionex Ultimate 3000, Thermo Scientific, Austria) was coupled to a high resolution QExactive orbitrap mass spectrometer (Thermo Scientific, Austria). Dried samples were resolved in 5µL 30% formic acid (FA) containing four synthetic peptides (10fmol each) and diluted with 40µL mobile phase A (98% H2O, 2% ACN, 0.1% FA). Each sample was recorded twice, 5µL were injected per analysis. The LC-method lasted 135 minutes with a 90min long gradient from 8-40% solvent B (80%ACN, 20%H¬2O, 0.1% FA) running over a 75µm x 50cm C-18 separation column (Dionex, Acclaim PepMap RSCL). The MS-method lasted 115min with the resolution set to 70000 and 17500, maximum injection time to 50ms and 75ms for MS1 and MS2, respectively. M/z was scanned from 400-1400 and a top 8 method was chosen for MS/MS analysis.PrideChristopher GernerUniversity of Vienna, Faculty of Chemistry, Department of Analytical ChemistryCOMPLETE28071820 Kreutz D, Bileck A, Plessl K, Wolrab D, Groessl M, Keppler BK, Meier SM, Gerner C. Response Profiling Using Shotgun Proteomics Enables Global Metallodrug Mechanisms of Action To Be Established. Chemistry. 2017 23(8):1881-1890 10.1002/chem.201604516University of Viennachristopher.gerner@univie.ac.atMass SpectrometryShotgun proteomicsColon CancerResponse profilingMetallodrugProteome profilingMechanism of actionFunctional protein groupshttps://www.ebi.ac.uk/pride/archive/projects/PXD004793Not availableProteome Discoverer 1.4 (Thermo Fisher Scientific, Austria) running Mascot 2.4 (Matrix Science, UK) was used for protein identification. Protein identification was achieved searching against the SwissProt Database (version August 2014 with 20 194 entries) allowing a mass tolerance of 10ppm for MS spectra and 50mmu for MS/MS spectra as well as a maximum of 2 missed cleavages. Furthermore, search criteria included carbamidomethylation on cysteins as fixed modification and methionine oxidation as well as N-terminal protein acetylation as variable modifications.ProteomicsHomo Sapiens (human)christopher.gerner@univie.ac.atBiologicalBiomedicalAustria10.6019/PXD004793Response profiling using shotgun proteomics for establishing global metallodrug mechanisms of action in two colon carcinoma cell lines, HCT116 and SW480, has been applied and evaluated with the clinically approved arsenic trioxide. Surprisingly, the complete established mechanism of action of arsenic trioxide was observed by protein regulations in SW480, but not HCT116 cells. Comparing the basal protein expression in the two cell lines revealed an 80 % convergence of protein identification, but with significant expression differences, which in turn seem to affect the extent of protein regulation. A clear-cut redox response was observed in SW480 cells upon treatment with arsenic, but hardly in HCT116 cells. Response profiling was then used to investigate four anti-cancer metallodrugs (KP46, KP772, KP1339 and KP1537). Proteome alterations were mapped to selected functional groups, including DNA repair, endocytosis, protection from oxidative stress, protection from endoplasmatic reticulum (ER) stress, cell adhesion and mitochondrial function. The present data suggest that knowledge of the mechanism of action of anti-cancer metallodrugs and improved patient stratification strategies are imperative for the design of clinical studies.Response Profiling Using Shotgun Proteomics Enables Global Metallodrug Mechanisms of Action To Be Established.Kreutz Dominique D, Bileck Andrea A, Plessl Kerstin K, Wolrab Denise D, Groessl Michael M, Keppler Bernhard K BK, Meier Samuel M SM, Gerner Christopher CAction, Generic Action., Peptidomicsextent, Regulations, DNA Oxidative, arsenicum, Oxidative Stress, l(1)VE614, HCT116, Peptidomics, Anhydride arsenieux, carcinoma cell, Antioxidative, Arsenolite, Antioxidative Stress, Gene, Nitrative Stress, Endocytoses, colon carcinoma cell, protein, nonselective vesicle endocytosis, protein-containing complex, HCT-116 Cells, mitochondrial, Damage, Social Controls, Arsenic-75, Stresses, Cut, protein polypeptide chains, Generic Action, Arsenic blanc, Client., Oxidative Nitrative, polypeptide chain, Oxidative DNA, l(1)7Ba, Oxidative, Stress Injury, l(1)7Bb, Taenia Coli, responsivity, As2O3, Nitro-Oxidative Stress, Appendix, Gene Products, Line, DNA Damage Response, Oxidative Cleavages, Mood, BOLD-100, Nitro-Oxidative Stresses, single organism cell adhesion, HCT116 Cell, protein aggregate, Oxidative Injury, Formal Social Controls, DNA Damage, Oxidative Damages, treatment, reactivity, Arsenic, Oxidative Injuries, Omental Appendix, Injury, Diarsenic Trioxide, Moods, cell adhesion molecule activity, Oxidative Cleavage, As, Tetra Arsenic Hexaoxide, posterior intestine, Arsenous oxide anhydride, proteins, Tetra-Arsenic Oxide, Oxidative DNA Damages, kf, sodium trans-(tetrachlorido-bis(1H-indazole)ruthenate(III)), CG11387, Anti-oxidative, Social, Adhesions, Oxidative Stress Injuries, Oxidative Stresses, DmelCG11387, Anti oxidative Stress, Arsenic trioxide, Oxidative DNA Damage, Antioxidative Stresses, Clients, Adhesion, disease management, Therapies, CT, HCT 116 Cell, SW480E, Trixenox, Trisenox, Therapy, plasma membrane invagination, completeness, Formal Social Control, Tetra-Arsenic Hexaoxide, protein complex, Affects, Proteins, Ct, Cell Lines, total expressed protein, KP1339, function, Anti-oxidative Stresses, Appendix Epiploica, Cell, hindgut, As4O6, Arsen, HCT116 cell, Oxidative Nitrative Stress, 33As, large bowel, native protein, natural protein, ATP synthase D chain, Social Control, Oxidative and Nitrosative Stress, arsenic, Oxidative Nitrative Stresses, Naonobin, Protein, arsenic(III) oxide, Arsenic(III) Oxide, Arsenous oxide, DNA Oxidative Damages, BcDNA:GH10590, Arsenous Anhydride, Omental Appendices, Arsenic Oxide (As2O3), Lines, Action, Arsenic Oxide (As4O6), Mitochondrial, Epistemology, HCT-116 Cell, Anti-oxidative Stress, HCT-116, DNA Oxidative Damage, HCT 116 Cells, Control, Tetraarsenic Hexaoxide, Diarsenic oxide, Appendices, Cell Adhesions, Arsenigen saure, patient, Omental, Controls, Cleavage, colonic carcinoma cell, Arsenic 75, Treatments, Protein Gene Products, Nitro-Oxidative, Gene Proteins, clear, hyaline, Therapeutic, Patient, COLON, HCT 116, Acide arsenieux, Cells, Stress, SW480, arsenico, Treatment, Oxidative Stress Injury, HCT-116 cell, regulation, response, Tetra Arsenic Oxide, DNA, colon, KP-1339, Nitro Oxidative Stress, Reticulums, Regulation, White arsenic, Proteomes, colon cancer cell, Tetraarsenic Oxide, Oxidative Damagesodium salt, CPD photolyase activity, ammonium formate, 13C-labeled, IL1BC, cadmium salt, artificial sequence, PhrB photolyase activity, Laboratory, CASP-1, rad, BOUND WATER, chronic obstructive pulmonary disease (COPD), SDH, Basodexan, magnesium formate, Thy-1, Apaf-1, zinc salt, Solvent, Long Term, HOH, 5730420M11Rik, dmTAF[[II]]230, SDS, Polypeptides, protein polypeptide chains, T22F8_160, 12-trihydroxy-24-oxocholan-24-yl)amino)propyl)-, cobalt(II) formate dihydrate, Method, Protease Inhibitor, ATGPR7, Chronic irreversible airway obstruction, 1, GRP8, 2, GRP7, 3, NUP96, 7, Il1bc, epithelium, pyruvic acid, (R*, SET, Divorced, Grain, amino acids, C79325, TFIID TAF250, hac-1, cel, N, chemical analysis., CAFL - Chronic airflow limitation, proteins, Divorces, T6G21.3, sodium trans-(tetrachlorido-bis(1H-indazole)ruthenate(III)), IL-1BC, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, DmelCG4299, salt, set, Dehydrated ethanol, Peptidohydrolase Inhibitor, disease (COPD), scientific observation, ACN, sample, Acn, autolysin activity, 12-trihydroxy-24-oxocholan-24-yl)amino)-, Inorganic, nickel salt, spiritus vini, chronic obstructive lung disease [Ambiguous], dTAF[[II]]230, Stars, Caspase-1 subunit p10, cobalt (+2) salt, Trypsin/K, anon-53Fa, TAF200, Longterm Effect, l(2)SH0173, Inorganic Chemistries, Procedure, alpha-amino carboxylic acids, CG3428, DmelCG7788, Absolute Alcohol, CHRONIC OBSTRUCTIVE AIRWAY DIS, H2O, common salt, sodium (4:1:1) salt, Dm1, magnesium salt, DmelCG42628, CHAPS, Hydrolase Inhibitor, dipyrimidine photolyase (photosensitive), University, Raps, Airflow Obstruction, [OEtH], CG6829, 5beta, dark/hac-1/dapaf-1, GLYCINE-RICH PROTEIN 8, Chronic Obstructive Airways Disease, N-dimethyl-N-(3-sulfopropyl)-3-(((3alpha, Acid, Chronic obstructive lung disease, HLA-DR-associated protein II, Amino acids, Antagonists, DI-2, I-2Dm, formate, Shwachman-Diamond type metaphyseal dysplasia, dyschromatosis symmetrica hereditaria 1, Dmel_CG15720, cromium (+3), Shwachman syndrome, Methodological, beta Trypsin, alcohol etilico, Methylcarbinol, I-2PP1, Speed, 7alpha, TAF-IBETA, F2G1.4, Taf250, OBSTRUCTIVE PULMONARY DISEASE (COPD), Drice, bacteriolytic toxin activity, ammonium (4:1) salt, Acids, TAF-Ibeta, Chemistries, Endopeptidase, Peptide Peptidohydrolase Inhibitor, DRICE, lead (+2) salt, STARS, 4-Dimercapto-2, TAF230, 10kDa, Cleland Reagent, F10B6_15, rac-Dithiothreitol, nickel formate dihydrate, lead formate, Effects, Endopeptidase Inhibitors, threo-1, DrIce, DrICE, Cleland's reagent, etanol, aluminum salt, CAO - Chronic airflow obstruction, 4-dimercapto-, Kern, Carbamide, CHRONIC OBSTRUCTIVE PULM DIS, Chronic obstructive pulmonary disease NOS, R*)-, protein-containing complex, thomson, Chalk, body system, 17alpha)-isomer, DmelCG5692, and RNA binding 1, F10B6.15, deoxyribodipyrimidine photolyase activity, CG7826, agua, mass-to-charge ratio, Chronic obstructive pulmonary disease finding, PULMONARY DISEASE (COPD), Gene Products, CG7835, CG42273, system, Peptide Hydrolase, Carmol, synthetic genetic interaction (sensu inequality), nucleo atomico, Technique, anatomical systems, dTAF[[II]]250, pins, Acinus, thallium (+1) salt, Longterm, cell, ethanol, PCE-2, beta-Trypsin, rubidium salt, F23A5.3, 4733401P19Rik, 2pp2a, Long-Term, methanoic acid, Antagonist, PINS, CG10574, Solution, CD156, acinusL, Study, Injectable, dTAF250, C2H5OH, 2PP2A, Protease Antagonists, Caspase-1 subunit p20, ATGRP7, acinusS, ATGRP8, congenital lipomatosis of pancreas, NEC, Kochsalz, dSET, dSet, Peptide Peptidohydrolase Inhibitors, Chronic, peptidos, SW480E, N-dimethyl-3-sulfo-N-(3-(((3alpha, 3-butanediol, measuring, dark/dapaf-1/hac-1, CG5692, Natriumpyruvat, chronic obstructive airways disease NOS, caspase 3, dApaf-1, Proteins, COAD, Clelands Reagent, T25, alpha-amino acids, BG:DS00004.13, potassium formate, CE-2, DSH, Mischung, copper (+2) salt, synthetic DNA, COLD - Chronic obstructive lung disease, buffer, Cell, chronic, Dithiothreitol, mKIAA0670, dTAF230, APAF1, native protein, Temperatures, Hsp10, Natriumchlorid, carbonyldiamide, Hac-1, I-2PP2A, cupric formate, chemical analysis, Dm I-2, Long Term Effects, alcool ethylique, TAF[[II]]250/230, synthetic, 5alpha, (COPD), chronic airway obstruction, NaCl, chronic obstructive, aluminum formate, Pins, CAL - Chronic airflow limitation, DTL, Cleland's, Taf[[II]]250, AU020952, DTT, RPE, lithium formate, holin, underdeveloped, ensemble, Separations, GR-RBP7, Striated muscle activator of Rho-dependent signaling, GR-RBP8, SWDS, Dark/Dapaf-1/HAC1, Shwachman-Bodian-Diamond syndrome, IL-1 beta-converting enzyme, Peptidohydrolase Inhibitors, Interleukin-1 beta-converting enzyme, CD156a, Inorganic Chemistry, Longterm Effects, p. pigmentosa retinae, ME-IV, plan specification, Cleland's Reagent, Gene Proteins, Peptidase, Antiprotease, Pancreatic insufficiency and bone marrow dysfunction, chronic obstructive lung disease (disorder), CG4346, SW480, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Peptide Hydrolase Inhibitors, KP-1339, [OH2], chronic obstructive pulmonary disease, Hac-1/Dark, IPP2A2, Endopeptidase Inhibitor, T22F8.160, Grain Alcohol, Meth, determination, and rna binding 2, Chronic Airflow Obstructions, DmelCG6829, Aminosaeure, Peptide Hydrolase Inhibitor, zinc formate, Amino acid, CG7788, crice, lead salt, protein, CG15720, pigmented epithelium, 1-hydroxyethane, Atomkern, alcohol, Ethanol, Techniques, hydroxide, halite, ammonium tetraformate, FBXO1, peptido, DmelCG3428, BANF, congenital, Nucleolar Protein, Alkohol, chronic obstructive airways disease NOS (disorder), Inhibitors, Min, BOLD-100, Apaf1, Chronic Obstructive Pulmonary Disease (COPD), Hydrolase Inhibitors, protein aggregate, ARK, Injectables, Effect, DmelCG42273, 3-hydroxy-5-estrane-17-carbonitrile, nucleus atomi, COLD (chronic obstructive lung disease), Nuclear Protein, rsh, peptides, NEC in ICD9CM_2006, TAF-I, Ethyl, E927b, long, 2610036I19Rik, 2610510L13Rik, E430039A18Rik, pigmented retina, hypoplasia, min, arc, mAPC, Aethanol, copper, [CH2Me(OH)], ark, DNA cyclobutane dipyrimidine photolyase activity, T1, Chronic airflow limitation, lipomatosis of pancreas, cloruro sodico, IGAAD, fSAP152, lithium salt, Thy1.1, Methodological Studies, SOLO DANCERS, Sputolysin, DmelCG10574, ICE, Ice, GLYCINE RICH PROTEIN 7, dihydridooxygen, Shwachman-Bodian syndrome, necrosis, dApaf1, dihydrogen oxide, Thy1.2, glycine-rich RNA-binding protein 8, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ammonium (2:1) salt, Long-Term Effects, Dmel_CG4346, inner salt, mt-cpn10, symmetric dyschromatosis of the extremities, CHRONIC, phapii, PRE, obstructive lung disease, rock salt, Alcohol, Peptidase Inhibitor, iCE, ice, D-Apaf-1, drice, Aminokarbonsaeure, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, aqua, Dmel_CG7826, AI836084, StF-IT-1, KP1339, Th, 4-dimercapto-2, Ethyl alcohol, TAFII-250, Peptide Peptidohydrolase, TAF250/230, Thermo Scientific, Airflow Obstructions, ur, pulmonary disease (COPD), carbamide, TAFII250, Cleland, retinal pigment, drIce, drICE, CHRONIC OBSTRUCTIVE, chronic obstructive pulmonary disease and allied conditions, Chronic airway disease, bacteriocin activity, NOS, ETHANOL, Sf3b10, nickel (+2) salt, retinal pigment layer, Dmel_CG7835, COPD NOS, Crystal, CHRONIC OBSTRUCTIVE LUNG DIS, Mnb, MNB, Amino Acid, Chronic airway obstruction, ammonium salt, EtOH, cold, MS/MS, ribosome-associated degradation, P45, familial reticulate acropigmentation of Dohi, cobaltous formate, hydrogen hydroxide, 3-Butanediol, hac1, CG4299, AW124434, natrii chloridum, CG17603, TAF[[II]], Methodological Study, acqua, REM3, organ system, dapaf-1S, Chronic Airflow Obstruction, R*)-1, H2NC(O)NH2, phr A photolyase activity, SYNTHETIC CONSTRUCT sequences, apaf-1, lysin activity, Peptidase Inhibitors, dapaf-1L, DNA-photoreactivating enzyme, COPD - Chronic obstructive pulmonary disease, SR3-5, copper salt, Antiproteases, chronic obstructive airways disease, p45, artificial, Polypeptide, Wasser, obstructive pulmonary disease (COPD), Inhibitor, RAD1, i2pp2a, chronic obstructive lung disease, COLD, 1728, d230, noyau atomique, Dapaf-1/HAC-1, Procedures, DISEASE (COPD), Reagent, 1110005L13Rik, cesium salt, Aminocarbonsaeure, rapsyn, Gene, Protease, dTAFII250, circadian rhythm, alpha-amino acid, ACINUS, photoreactivating enzyme activity, EfW1, PHAPII, Buffer, formic acid, Dark/Hac-1/dApaf1, Karbamid, Aethylalkohol, Cold, method, Hac1, potassium salt, CD90, Dark/Hac-1/dApaf-1, Pulmonary Disease, polypeptide chain, reduced, dmTAF1, Ms1, Taf230, Injection, 14C-labeled, method used in an experiment, Harnstoff, Tina, Studies, Protease Antagonist, stratum pigmentosa retinae, tiny, Separated, Pro-Mega, TAF250, nuclei, Cold Temperatures, Taf200, MOS3, Glass, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, PRECOCIOUS, MS1, Absolute, MS2, nucleo, noyau, ipp2a2, dapaf-1, chlorure de sodium, synthetic genetic interaction defined by inequality, Taf1p, dapaf, dark, eau, calcium formate, Chronic Obstructive, nucleus, DARK, taf-ibeta, male sterility 1, cromium (+3) salt, Long-Term Effect, 12alpha)-3, TAF, dArk, Dapaf-1, F23A5_3, sodium formate, COPD, 1-Propanaminium, small, 7alpha)-3, COAD - Chronic obstructive airways disease, DYRK1, TAF[[II]]250, CG42628, AU043053, nickel formate, Thy-1.2, protein complex, cholic acid sulfobetaine1-Propanaminium, not elsewhere classified, igaad, strontium formate, l(3)84Ab, artificial gene, apaf1, strontium salt, Peptide, PULM DIS CHRONIC OBSTRUCTIVE, Chronic obstructive pulmonary disease finding (finding), group, Dithiotreitol, MODIFIER OF SNC1, natural protein, p230, Protein, 3-(3-cholamidopropyl)dimethylammoniumpropane sulfonate, DL-threo-1, deoxyribonucleic photolyase activity, I2PP2A, TFIID, table salt, Nuclear, Dyrk1, CES2A1, GLYCINE-RICH RNA-BINDING PROTEIN 7, Dark, connected anatomical system, (3alpha, Dark/Apaf-I, tandem MS, chronic obstructive airway disease, Ethyl Alcohol, Temperature, Separation, TAF[[II]]230, PRSS, uree, photolyase activity, MALE STERILITY 1 PROTEIN, Dops, CC1, Tripcellim, TAF[II]250, Nucleolar Proteins, Amino, CGI-97, synthetic constructs, dApaf-1/DARK/HAC-1, sample population, chromic formate, Protein Gene Products, Interleukin-1 beta convertase, Trypure, dSET/TAF-Ibeta, hydroxyethane, 2610030F17Rik, DmelCG17603, 3.4.22.36, calcium salt, cold (chronic obstructive lung disease), Peptid, RAD, Rad, Chronic Obstructive Lung Disease, assay, Nucleolar, SCH, AA407739, Runnings, dAPAF-1, TAF1, 3-OHECNDNA Oxidative, mode of action, arsenicum, pharmacodynamics, HCT116, carcinoma cell, Arsenolite, Nitrative Stress, protein, nonselective vesicle endocytosis, Tumor, HCT-116 Cells, Damage, Social Controls, Cut, protein polypeptide chains, Generic Action, Arsenic blanc, judicial aspects, Oxidative DNA, l(1)7Ba, Oxidative, l(1)7Bb, As2O3, Nitro-Oxidative Stress, Line, BOLD-100, Nitro-Oxidative Stresses, protein aggregate, Oxidative Injury, Formal Social Controls, DNA Damage, treatment, Oxidative Injuries, Moods, Oxidative Cleavage, medicolegal aspects, As, Arsenous oxide anhydride, proteins, Oxidative DNA Damages, sodium trans-(tetrachlorido-bis(1H-indazole)ruthenate(III)), CG11387, Anti-oxidative, Social, Adhesions, Oxidative Stress Injuries, Oxidative Stresses, malignant neoplasm, Adhesion, disease management, Therapies, CT, Malignancies, juridical aspects, HCT 116 Cell, Trixenox, Tumors, Trisenox, Therapy, Ct, KP1339, As4O6, HCT116 cell, 33As, Benign, Redox, ATP synthase D chain, Oxidative and Nitrosative Stress, arsenic, arsenic(III) oxide, Arsenic(III) Oxide, DNA Oxidative Damages, BcDNA:GH10590, Arsenous Anhydride, Lines, Action, Arsenic Oxide (As4O6), Mitochondrial, Epistemology, HCT-116, jurisprudence, HCT 116 Cells, Control, Tetraarsenic Hexaoxide, Benign Neoplasms, Arsenigen saure, Controls, Treatments, Malignant Neoplasms, Nitro-Oxidative, hyaline, Patient, Acide arsenieux, Cells, arsenico, Oxidative Stress Injury, litigation, Tetra Arsenic Oxide, DNA, colon, Reticulums, Regulation, White arsenic, Proteomes, colon cancer cell, Oxidation Reduction, Oxidative Damage, Regulations, Oxidative Stress, l(1)VE614, ordinances, Peptidomics, Anhydride arsenieux, Antioxidative, Neoplasms, Benign Neoplasm, Antioxidative Stress, Gene, Endocytoses, colon carcinoma cell, protein-containing complex, Malignant, mitochondrial, Arsenic-75, Stresses, legislation and jurisprudence, laws, civil suits, Client., Oxidative Nitrative, polypeptide chain, Stress Injury, Gene Products, DNA Damage Response, Oxidative Cleavages, Mood, single organism cell adhesion, HCT116 Cell, Oxidative Damages, Arsenic, Injury, Malignancy, Diarsenic Trioxide, cell adhesion molecule activity, Tetra Arsenic Hexaoxide, Tetra-Arsenic Oxide, kf, Neoplasias, mechanism of action, DmelCG11387, Anti oxidative Stress, Arsenic trioxide, Oxidative DNA Damage, Antioxidative Stresses, Clients, lawsuits, regulations, statutes, SW480E, Cancer, data, Malignant Neoplasm, plasma membrane invagination, Formal Social Control, Tetra-Arsenic Hexaoxide, protein complex, Affects, Proteins, Cell Lines, total expressed protein, function, Anti-oxidative Stresses, Cell, Arsen, Oxidative Nitrative Stress, MT, native protein, natural protein, Social Control, government regulations, Oxidative Nitrative Stresses, Naonobin, Protein, Neoplasm, Arsenous oxide, legal aspects, Arsenic Oxide (As2O3), HCT-116 Cell, primary cancer, Anti-oxidative Stress, DNA Oxidative Damage, Diarsenic oxide, Cell Adhesions, patient, Cancers, Cleavage, colonic carcinoma cell, Arsenic 75, malignant tumor, court decisions, Protein Gene Products, Gene Proteins, pharmacologic action, clear, Therapeutic, HCT 116, Stress, SW480, Treatment, HCT-116 cell, regulation, KP-1339, Nitro Oxidative Stress, Neoplasia, Tetraarsenic OxideTransitional Epithelial Cell, Transitional, Adenomatous Epithelial Cell, reactivity, Action, Squamous Cells, Adenomatous Epithelial Cells, Squamous Cell, Nuclear Protein, Epithelial Cell, Peptidomics, Glandular Epithelial Cell., Proteins, Glandular Epithelial Cells, Adenomatous, KP1339, Nucleolar Proteins, Adenomatous Epithelial, Glandular Epithelial, Squamous, Glandular, Transitional Epithelial, sodium trans-(tetrachlorido-bis(1H-indazole)ruthenate(III)), Cell, Generic Action, Squamous Epithelial Cells, Cuboidal Glandular Epithelial Cells, Epithelial Cells, Transitional Epithelial Cells, responsivity, Nucleolar Protein, Protein, Cells, SW480, Nuclear, BOLD-100, response, Columnar Glandular Epithelial Cells, KP-1339, Nucleolar, SW480E, Squamous Epithelial Cell, Squamous Epithelial, Epithelial2-amino-4-(methylsulfanyl)butanoic acid, AW549739, DL-Methionine, protein complex, Proteins, 2-Amino-4-(methylthio)butyric acid, L Isomer, FBN, Gene, protein, protein-containing complex, L-Isomer, ACMICD, protein polypeptide chains, L-Isomer Methionine, Methionine, variable., native protein, natural protein, polypeptide chain, ECTOL1, Protein, Gene Products, L-Methionine, MFS1, Methionin, Hmet, protein aggregate, WMS, tandem MS, Pedameth, Data Base, WMS2, Met, C79691, MS/MS, MS2, M, protein amino acid acetylation, Sciences, MASCOT, proteins, MASS, Lccp, Protein Gene Products, OCTD, mKIAA0989, Gene Proteins, 2-amino-4-(methylthio)butanoic acid, SSKS, alpha-amino-gamma-methylmercaptobutyric acid, GPHYSD2, metionina, Runnings, Racemethionine, Liquimeth, SGSfalseResponse Profiling Using Shotgun Proteomics Enables Establishing Global Metallodrug Mechanisms of Action - nuclear proteins of KP1339-treated SW480 epithelial cellsResponse profiling using shotgun proteomics for establishing global metallodrug mechanisms of action in two colon carcinoma cell lines, HCT116 and SW480, was applied and evaluated with the clinically approved arsenic trioxide. Surprisingly, the complete established mechanism of action of arsenic trioxide was observed by protein regulations in SW480, but not in HCT116 cells. Comparing the basal protein expression in the two cell lines revealed an 80% convergence of protein identifications, but with significant expression differences, which in turn seem affect the extent of protein regulation. For example, while a clear-cut redox response was observed in SW480 cells upon arsenic treatment, such an effect was lacking in HCT116 cells and the latter express drastically higher levels of the involved redox proteins. Response profiling was then used to investigate four anticancer metallodrugs (KP46, KP772, KP1339 and KP1537) by means of functional groups of proteins and mapped their effects according to DNA repair, endocytosis, protection from oxidative stress, protection from endoplasmatic reticulum (ER) stress, cell adhesion and mitochondrial function. We were able to characterize the global effects of these metallodrugs on the proteome and generate hypotheses on hitherto unrecognized mechanisms. Significant differences in the two colon cell lines strongly suggest that knowledge of mechanistic hallmarks of anticancer metallodrug action are imperative for the design of clinical studies and that outcome may be enhanced by means of patient stratification strategies according to these hallmarks.2022-02-242016-08-15PXD004793NEWT:3555NEWT:71647NEWT:330879NEWT:35554NCBITaxon:12939NEWT:32046NEWT:544496NEWT:59529NEWT:2042546NEWT:32049NEWT:1392696NEWT:259447NEWT:295546NEWT:45351NEWT:445974NEWT:43179NEWT:180454NEWT:5722NCBITaxon:1280NEWT:112503NEWT:1129NEWT:309807NEWT:10245NEWT:55153NEWT:89184NEWT:309800NEWT:281395NEWT:1211601NEWT:876138NEWT:44271NEWT:193516NEWT:351581NEWT:43186NEWT:428146NEWT:1117NEWT:498257NEWT:10036NEWT:1590NEWT:498019NEWT:1351NEWT:1438992NEWT:1352NEWT:2649997NEWT:1147161NEWT:661410NEWT:638632NEWT:263737NEWT:224326NEWT:1333499NEWT:376619NCBITaxon:79857NEWT:1096976NEWT:5702NEWT:95648NEWT:1589NEWT:135622NEWT:1349NEWT:35786NEWT:1580NEWT:399784NEWT:96731NEWT:383379NEWT:1401257NEWT:418106NEWT:10029NEWT:913645NEWT:44491NEWT:641809NEWT:27933NEWT:556484NEWT:317447NEWT:4688NEWT:7955NEWT:7719NEWT:7959NEWT:2261NEWT:868565NEWT:31156NEWT:3112NEWT:79329NEWT:4442NEWT:192875NEWT:12637NEWT:59729NEWT:2164133NEWT:284218NEWT:295105NEWT:108061NEWT:60711NEWT:1316931NEWT:224308NEWT:3347NEWT:511145NEWT:160621NEWT:212790NEWT:931281NEWT:4432NEWT:5762NEWT:5763NEWT:658457NEWT:1310161NEWT:77133NEWT:295358NEWT:145481NEWT:29058NCBITaxon:79824NEWT:2246NEWT:2652724NEWT:5757NEWT:68415NCBITaxon:4563NEWT:5755NEWT:44688NEWT:44689NEWT:44447NEWT:752555NEWT:498211NEWT:5759NEWT:347256NEWT:1736231NEWT:5518NEWT:398007NEWT:1527468NEWT:1392NEWT:498217NEWT:498216NEWT:2242NEWT:11320NEWT:286NEWT:391619NEWT:246196NEWT:287NEWT:246197NEWT:145458NEWT:633149NEWT:1149786NEWT:10239NEWT:68895NEWT:44685NEWT:161934NEWT:4897NEWT:1148NEWT:5744NEWT:72901NEWT:213863NEWT:5508NEWT:3329NEWT:5507NEWT:410661NEWT:55571NEWT:35500NEWT:1140NCBITaxon:2157NEWT:1143NEWT:4896NEWT:1287689NEWT:1390NEWT:11557NEWT:1094343NEWT:1462472NEWT:1336795NEWT:644042NEWT:294NEWT:1773NEWT:1182590NEWT:3712NEWT:82380NEWT:3711NEWT:935293NEWT:375146NEWT:2065263NEWT:177437NEWT:1772NEWT:10418NEWT:118698NEWT:1616117NEWT:263NEWT:118696NEWT:34865NEWT:52283NEWT:11988NEWT:284812NEWT:8175NEWT:400667NEWT:43330NEWT:1603293NEWT:408169NEWT:44664NEWT:47946NEWT:3702NEWT:1245466NEWT:243277NEWT:1246791NEWT:7067NEWT:118694NEWT:586722NEWT:2850NEWT:118691NEWT:34871NEWT:33548NEWT:274NEWT:7070NCBITaxon:287NEWT:408172NEWT:408170NEWT:96794NEWT:3708NEWT:332648NEWT:44670NEWT:536231NEWT:376219NEWT:219813NEWT:1510NEWT:1436733NEWT:460519NEWT:1247411NEWT:1515NEWT:572307NEWT:1432138NEWT:1424507NEWT:1194599NEWT:272844NEWT:1303443NEWT:333760NEWT:56636NEWT:1513458NEWT:1233681NCBITaxon:40559NEWT:506599NEWT:2853422NEWT:81077NEWT:84588NEWT:1679718NEWT:480NEWT:65349NEWT:67767NEWT:46835NEWT:109757NEWT:582580NEWT:300852NEWT:1502NEWT:128017NEWT:376686NEWT:95486NEWT:508771NEWT:1883446NEWT:253NCBITaxon:2759NEWT:1233435NEWT:93061NEWT:93062NEWT:34613NCBITaxon:4932NEWT:109760NEWT:29031NEWT:943274NEWT:644223NEWT:235443NEWT:108458NEWT:5936NEWT:272623NEWT:272624NEWT:320637NEWT:886559NEWT:3750NEWT:55521NEWT:983964NEWT:118499NEWT:11706NEWT:32644NEWT:527796NEWT:1130798NEWT:55529NEWT:499175NEWT:109779NEWT:3745NEWT:1715989NCBITaxon:4751NEWT:476272NEWT:3747NEWT:195051NEWT:3988NEWT:1116234NEWT:561007NEWT:1255228NEWT:649908NEWT:410289NEWT:373153NEWT:3983NEWT:203696NEWT:352472NEWT:97441NEWT:1071661NEWT:1202532NEWT:360094NEWT:1408223NEWT:470NEWT:1408224NEWT:41364NEWT:5911NEWT:1313NEWT:1218097NEWT:1080348NCBITaxon:50557NEWT:1314NEWT:39251NEWT:39491NEWT:212142NCBITaxon:5811NEWT:29491NEWT:101841NEWT:153481NEWT:2014887NEWT:33952NEWT:445NEWT:153009NEWT:261756NEWT:571256NEWT:40483NEWT:63366NEWT:63367NEWT:688333NEWT:215402NCBITaxon:548681NEWT:318586NCBITaxon:5820NEWT:1547NEWT:272634NEWT:198107NEWT:9031NEWT:27292NEWT:1872122NEWT:1308NEWT:7091NEWT:1034015NEWT:760568NEWT:141262NEWT:108931NEWT:1293497NEWT:1055524NEWT:4087NEWT:9778NEWT:306NEWT:150475NEWT:303NEWT:267872NEWT:97477NEWT:7111NEWT:347515NEWT:172269NEWT:9534NEWT:6269NEWT:5180NEWT:256737NEWT:4090NEWT:4092NEWT:9541NEWT:8694NEWT:4093NEWT:33936NEWT:4096NEWT:8692NEWT:2903NEWT:185579NEWT:941442NEWT:536088NEWT:13076NEWT:1226408NEWT:7108NEWT:40479NEWT:43989NEWT:4076NEWT:142615NEWT:317NEWT:1006581NEWT:33940NEWT:885318NEWT:39488NEWT:550NEWT:4081NEWT:273068NEWT:554NEWT:98334NEWT:451516NEWT:552NEWT:231663NEWT:4084NEWT:1325291NEWT:63577NEWT:36185NEWT:1225786NEWT:7574NEWT:1715256NEWT:30640NEWT:575412NEWT:929793NEWT:1507179NEWT:29204NEWT:28112NEWT:114155NEWT:6494NEWT:6491NEWT:507601NEWT:520NEWT:186441NEWT:634955NEWT:643680NEWT:214092NCBITaxon:6157NEWT:6239NEWT:13095NEWT:162425NEWT:104105NEWT:216257NEWT:102169NEWT:208893NEWT:9986NEWT:4054NEWT:8654NEWT:8658NEWT:1268063NEWT:8657NEWT:8655NEWT:5147NEWT:98351NEWT:1263854NEWT:118503NEWT:2059687NEWT:160488NEWT:28104NEWT:207559NEWT:407821NCBITaxon:2NEWT:85057NEWT:985076NEWT:568708NEWT:1215323NEWT:986NEWT:52641NEWT:7159NEWT:267671NEWT:28532NEWT:7160NEWT:353152NEWT:8496NEWT:7165NEWT:1257118NEWT:27448NEWT:40674NEWT:1194669NEWT:235612NEWT:243230NEWT:443906NEWT:1080772NEWT:519NEWT:8479NEWT:8485NEWT:6063NEWT:49240NEWT:1328388NEWT:667127NEWT:9557NEWT:9315NEWT:6289NEWT:377586NEWT:6287NEWT:38569NEWT:300641NEWT:727NEWT:39655NEWT:9796NEWT:9554NEWT:725NEWT:7137N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