{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002116","ANALYSIS_ID":"AN003464","VERSION":"1","CREATED_ON":"March 23, 2022, 2:34 am"},

"PROJECT":{"PROJECT_TITLE":"Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt based drugs","PROJECT_SUMMARY":"Pt based drugs play a very important role in current cancer treatment; yet their cellular and mechanistic aspects are not fully understood. NMR metabolomics provides a powerful tool to investigate the metabolic perturbations induced by Pt drugs in cancer cells and decipher their meaning in relation to the presumed molecular mechanisms. We have carried out a systematic and comparative NMR metabolomics study to analyze the responses of A2780 human ovarian cancer cells to the main clinically established Pt drugs, i.e. cisplatin, carboplatin and oxaliplatin, with a particular attention for the oxaliplatin/cisplatin comparison in view of recently described mechanistic differences. Notably, NMR analysis revealed some moderate and consistent changes in the metabolomic profiles of A2780 cells treated with the 3 Pt drugs with respect to controls but only very small differences among them. Beyond the expected alterations at the level of the nucleic acids the observed changes highlight in all cases induction of a significant ER stress. Owing to the clinical relevance of platinum resistance the behavior of a cisplatin resistant A2780 cancer cell line upon cisplatin treatment was also evaluated.","INSTITUTE":"University of Florence","DEPARTMENT":"Department of Chemistry","LABORATORY":"Metabolomics","LAST_NAME":"Ghini","FIRST_NAME":"Veronica","ADDRESS":"via Luigi Sacconi 6, 50019, Sesto Fiorentino, Italy","EMAIL":"ghini@cerm.unifi.it","PHONE":"+39 3922800462"},

"STUDY":{"STUDY_TITLE":"Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt based drugs","STUDY_SUMMARY":"Pt based drugs play a very important role in current cancer treatment; yet their cellular and mechanistic aspects are not fully understood. NMR metabolomics provides a powerful tool to investigate the metabolic perturbations induced by Pt drugs in cancer cells and decipher their meaning in relation to the presumed molecular mechanisms. We have carried out a systematic and comparative NMR metabolomics study to analyze the responses of A2780 human ovarian cancer cells to the main clinically established Pt drugs, i.e. cisplatin, carboplatin and oxaliplatin, with a particular attention for the oxaliplatin/cisplatin comparison in view of recently described mechanistic differences. Notably, NMR analysis revealed some moderate and consistent changes in the metabolomic profiles of A2780 cells treated with the 3 Pt drugs with respect to controls but only very small differences among them. Beyond the expected alterations at the level of the nucleic acids the observed changes highlight in all cases induction of a significant ER stress. Owing to the clinical relevance of platinum resistance the behavior of a cisplatin resistant A2780 cancer cell line upon cisplatin treatment was also evaluated.","INSTITUTE":"University of Florence","DEPARTMENT":"Department of Chemistry","LABORATORY":"Metabolomics","LAST_NAME":"Ghini","FIRST_NAME":"Veronica","ADDRESS":"via Luigi Sacconi 6","EMAIL":"turano@cerm.unifi.it","PHONE":"+390554574266"},

"SUBJECT":{"SUBJECT_TYPE":"Cultured cells","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","CELL_STRAIN_DETAILS":"A2780 ovarian cancer cells"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"Cell-Carbo-24h-1",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Carbo-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Carbo-24h-2",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Carbo-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-CARBO-24h-4",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-CARBO-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Carbo-48h-1",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Carbo-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Carbo-48h-3",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Carbo-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Carbo-48h-4",
"Factors":{"sample_type":"lysate","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Carbo-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-24h-1",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-24h-2",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-CIS-24h-4",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-CIS-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-48h-1",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-48h-3",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-48h-4",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-24h-1",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-24h-2",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-24h-4",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-48h-1",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-48h-3",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Ctr-48h-4",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Ctr-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Oxa-24h-1",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Oxa-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Oxa-24h-2",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Oxa-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-OXA-24h-4",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-OXA-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Oxa-48h-1",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Oxa-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Oxa-48h-3",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Oxa-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Oxa-48h-4",
"Factors":{"sample_type":"lysate","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Oxa-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-R-48h-1-1411",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-R-48h-1-1411"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-R-48h-2-2110",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-R-48h-2-2110"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cis-R-48h-3-2810",
"Factors":{"sample_type":"lysate","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cis-R-48h-3-2810"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cont-R-48h-1-1411",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cont-R-48h-1-1411"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cont-R-48h-2-2110",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cont-R-48h-2-2110"}
},
{
"Subject ID":"-",
"Sample ID":"Cell-Cont-R-48h-3-2810",
"Factors":{"sample_type":"lysate","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"Cell-Cont-R-48h-3-2810"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CARBO-24h-1",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CARBO-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CARBO-24h-2",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CARBO-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Carbo-24h-4",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Carbo-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CARBO-48h-1",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CARBO-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CARBO-48h-3",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CARBO-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CARBO-48h-4",
"Factors":{"sample_type":"medium","treatment_type":"carboplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CARBO-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-24h-1",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-24h-2",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Cis-24h-4",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Cis-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-48h-1",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-48h-3",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-48h-4",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CTR-24h-1",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CTR-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CTR-24h-2",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CTR-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Ctr-24h-4",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Ctr-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CTR-48h-1",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CTR-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CTR-48h-3",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CTR-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CTR-48h-4",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CTR-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-OXA-24h-1",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-OXA-24h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-OXA-24h-2",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-OXA-24h-2"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Oxa-24h-4",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"24","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Oxa-24h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-OXA-48h-1",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-OXA-48h-1"}
},
{
"Subject ID":"-",
"Sample ID":"SN-OXA-48h-3",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-OXA-48h-3"}
},
{
"Subject ID":"-",
"Sample ID":"SN-OXA-48h-4",
"Factors":{"sample_type":"medium","treatment_type":"oxaliplatin","treatment_time":"48","cell_line":"A2780"},
"Additional sample data":{"RAW_FILE_NAME":"SN-OXA-48h-4"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-R-48h-1-1411",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-R-48h-1-1411"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-R-48h-2-2110",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-R-48h-2-2110"}
},
{
"Subject ID":"-",
"Sample ID":"SN-CIS-R-48h-3-2810",
"Factors":{"sample_type":"medium","treatment_type":"cisplatin","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-CIS-R-48h-3-2810"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Cont-R-48h-1-1411",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Cont-R-48h-1-1411"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Cont-R-48h-2-2110",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Cont-R-48h-2-2110"}
},
{
"Subject ID":"-",
"Sample ID":"SN-Cont-R-48h-3-2810",
"Factors":{"sample_type":"medium","treatment_type":"control","treatment_time":"48","cell_line":"A2780cp"},
"Additional sample data":{"RAW_FILE_NAME":"SN-Cont-R-48h-3-2810"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"A2780 cells were purchase from Sigma-Aldrich and derived from the European Collection of Authenticated Cell Culture (human ovarian carcinoma; catalogue no.: 93112519; lot no.13J012, passage no.: P + 9). A2780cp cells were kindly provided by Dr Simona Bracini and were obtained via prolonged exposition to sub-lethal dose of cisplatin. Cells were maintained in RPMI1640 medium supplemented with 2 mM glutamine, 10% of FCS and antibiotics at 37 °C in a 5% CO2 atmosphere and sub-cultured twice weekly. Split 1:5 (3–6 × 10^4 cells per mL).","SAMPLE_TYPE":"Cultured cells","STORAGE_CONDITIONS":"-80℃"},

"TREATMENT":{"TREATMENT_SUMMARY":"For drug treatment, 2.7 *10^6 A2780 cells were seeded in p100 plate and after 24 hours were exposed to a concentration of the three Pt-drugs, i.e. CIS, OXA and CARBO equal to their 72 h-exposure IC50 value (2.5, 55 and 0.46 uM, respectively). The drug incubations were stopped at two different time points, 24 h and 48 h. The A2780cp cells were exposed to a concentration of cisplatin equal to their 72 h-exposure IC50 value (15 uM). The drug incubation was stopped after 48 h of treatment.","TREATMENT":"Cisplatin, carboplatin and oxaliplatin","CELL_MEDIA":"RPMI1640"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Frozen samples were thawed at room temperature and shaken before use. For cell lysates, 50 μl of 2H2O were added to 450 μl of each lysate sample. In the case of cell culture media, 300 μl of sodium phosphate buffer (70 mM Na2HPO4; 20% v/v 2H2O; 4.6 mM TMSP, pH 7.4) was added to 300 μl of each medium sample. The mixtures were homogenized by vortexing for 30 s and transferred into 5 mm NMR tubes (Bruker BioSpin srl) for analysis."},

"ANALYSIS":{"ANALYSIS_TYPE":"NMR","LABORATORY_NAME":"Metabolomics"},

"NM":{"INSTRUMENT_NAME":"Bruker Advance 600 MHZ","INSTRUMENT_TYPE":"FT-NMR","NMR_EXPERIMENT_TYPE":"1D-1H","SPECTROMETER_FREQUENCY":"600 MHz","NMR_TUBE_SIZE":"5,00 mm","WATER_SUPPRESSION":"water presaturation","TEMPERATURE":"300 K for lysates and 31o for media","NMR_RESULTS_FILE":"ST002116_AN003464_Results.txt UNITS:ppm"}

}