Summary of Study ST003260

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002023. The data can be accessed directly via it's Project DOI: 10.21228/M8423Z This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003260
Study TitleExploration of RSL3-induced and Chlorido[N,N’-disalicylidene-1,2-phenylenediamine]iron(III) complex-induced changes in the lipidome of MDA-MB-231 breast cancer cells
Study SummaryChlorido[N,N’-disalicylidene-1,2-phenylenediamine]iron(III) complexes (SCs) exhibit potent anti-cancer properties through incompletely understood molecular mechanisms. Here, we treated human MDA-MB-231 triple-negative breast cancer cells with the glutathione peroxidase (GPX)4 inhibitor RSL3 or chlorido[N,N’-disalicylidene-1,2-phenylenediamine]iron(III) complexes (SCs) and analyzed their phospholipid profile by targeted lipidomics. SCs decreased the cellular proportion of polyunsaturated fatty acids (PUFAs) in phospholipids, which barely changed upon short-term treatment with RSL3.
Institute
University of Innsbruck
DepartmentMichael Popp Institute
Last NameKoeberle
First NameAndreas
AddressMitterweg 24, Innsbruck, Tyrol, 6020, Austria
EmailAndreas.Koeberle@uibk.ac.at
Phone+43 512 507 57903
Submit Date2024-06-12
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2024-06-27
Release Version1
Andreas Koeberle Andreas Koeberle
https://dx.doi.org/10.21228/M8423Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002023
Project DOI:doi: 10.21228/M8423Z
Project Title:Iron(III)-salophene catalyzes redox cycles that induce phospholipid peroxidation and deplete cancer cells of ferroptosis-protecting cofactors
Project Summary:Ferroptosis, regulated by glutathione peroxidase 4 and redox cycles, offers new cancer treatment strategies. Chlorido[N,N’-disalicylidene-1,2-phenylenediamine]iron(III) complexes (SCs, compounds 1-3) exhibit potent anti-cancer effects by inducing ferroptosis, apoptosis, or necroptosis, including in therapy-resistant cancers. Our study shows that SCs favor ferroptosis in triple-negative breast cancer cells and are effective against invasive, chemo- or radioresistant cell lines. Redox lipidomics indicates that SCs initiate cell death through extensive oxidation of arachidonic and adrenic acids in membrane phospholipids. Mechanistically, SCs catalyze one-electron transfer reactions, reducing Fe(III) to Fe(II), forming oxo-bridged dimers, and generating organic radicals using hydrogen peroxide. This process depletes NADPH, oxidizes membrane phospholipids, and disrupts cellular detoxification of phospholipid hydroperoxides.
Institute:University of Innsbruck
Department:Michael Popp Institute
Last Name:Koeberle
First Name:Andreas
Address:Mitterweg 24, Innsbruck, Tyrol, 6020, Austria
Email:Andreas.Koeberle@uibk.ac.at
Phone:+43 512 507 57903
Funding Source:Austrian Science Fund (FWF) (P 36299), Phospholipid Research Center Heidelberg (AKO-2022-100/2-2)
Publications:DOI : https://doi.org/10.1016/j.redox.2024.103257
Contributors:Fengting Su, Andreas Koeberle

Subject:

Subject ID:SU003380
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Treatment time point
SA354103210324_Rescue_Gust_compounds_2h_n2_Ti41_10uM_T58Breast cancer cells 10 µM Comp. 1 2 h
SA354104210324_Rescue_Gust_compounds_2h_n1_Ti41_10uM_T46Breast cancer cells 10 µM Comp. 1 2 h
SA354105210324_Rescue_Gust_compounds_2h_n3_Ti41_10uM_T70Breast cancer cells 10 µM Comp. 1 2 h
SA354106210324_Rescue_Gust_compounds_2h_n1_Ti41_F_10uM_T49Breast cancer cells 10 µM Comp. 2 2 h
SA354107210324_Rescue_Gust_compounds_2h_n2_Ti41_F_10uM_T61Breast cancer cells 10 µM Comp. 2 2 h
SA354108210324_Rescue_Gust_compounds_2h_n3_Ti41_F_10uM_T73Breast cancer cells 10 µM Comp. 2 2 h
SA354109210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_10uM_T76Breast cancer cells 10 µM Comp. 3 2 h
SA354110210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_10uM_T64Breast cancer cells 10 µM Comp. 3 2 h
SA354111210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_10uM_T52Breast cancer cells 10 µM Comp. 3 2 h
SA354115210309_MDA_Timecourse_RSL3_n2_24h_RSL3_10uM_24Breast cancer cells 10 µM RSL3 24 h
SA354116210309_MDA_Timecourse_RSL3_n3_24h_RSL3_10uM_36Breast cancer cells 10 µM RSL3 24 h
SA354117210309_MDA_Timecourse_RSL3_n1_24h_RSL3_10uM_12Breast cancer cells 10 µM RSL3 24 h
SA354112210309_MDA_Timecourse_RSL3_n3_2h_RSL3_10uM_27Breast cancer cells 10 µM RSL3 2 h
SA354113210309_MDA_Timecourse_RSL3_n2_2h_RSL3_10uM_15Breast cancer cells 10 µM RSL3 2 h
SA354114210309_MDA_Timecourse_RSL3_n1_2h_RSL3_10uM_3Breast cancer cells 10 µM RSL3 2 h
SA354118210309_MDA_Timecourse_RSL3_n3_4h_RSL3_10uM_30Breast cancer cells 10 µM RSL3 4 h
SA354119210309_MDA_Timecourse_RSL3_n2_4h_RSL3_10uM_18Breast cancer cells 10 µM RSL3 4 h
SA354120210309_MDA_Timecourse_RSL3_n1_4h_RSL3_10uM_6Breast cancer cells 10 µM RSL3 4 h
SA354121210309_MDA_Timecourse_RSL3_n2_6h_RSL3_10uM_21Breast cancer cells 10 µM RSL3 6 h
SA354122210309_MDA_Timecourse_RSL3_n3_6h_RSL3_10uM_33Breast cancer cells 10 µM RSL3 6 h
SA354123210309_MDA_Timecourse_RSL3_n1_6h_RSL3_10uM_9Breast cancer cells 10 µM RSL3 6 h
SA354076210324_Rescue_Gust_compounds_2h_n1_Ti41_1uM_T44Breast cancer cells 1 µM Comp. 1 2 h
SA354077210324_Rescue_Gust_compounds_2h_n3_Ti41_1uM_T68Breast cancer cells 1 µM Comp. 1 2 h
SA354078210324_Rescue_Gust_compounds_2h_n2_Ti41_1uM_T56Breast cancer cells 1 µM Comp. 1 2 h
SA354079210324_Rescue_Gust_compounds_2h_n2_Ti41_F_1uM_T59Breast cancer cells 1 µM Comp. 2 2 h
SA354080210324_Rescue_Gust_compounds_2h_n3_Ti41_F_1uM_T71Breast cancer cells 1 µM Comp. 2 2 h
SA354081210324_Rescue_Gust_compounds_2h_n1_Ti41_F_1uM_T47Breast cancer cells 1 µM Comp. 2 2 h
SA354082210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_1uM_T62Breast cancer cells 1 µM Comp. 3 2 h
SA354083210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_1uM_T74Breast cancer cells 1 µM Comp. 3 2 h
SA354084210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_1uM_T50Breast cancer cells 1 µM Comp. 3 2 h
SA354085210324_Rescue_Gust_compounds_2h_n3_RSL3_1uM_Ferrostatin1_3uM_T67Breast cancer cells 1 µM RSL3 + 3 µM Ferrostatin 2 h
SA354086210324_Rescue_Gust_compounds_2h_n1_RSL3_1uM_Ferrostatin1_3uM_T43Breast cancer cells 1 µM RSL3 + 3 µM Ferrostatin 2 h
SA354087210324_Rescue_Gust_compounds_2h_n2_RSL3_1uM_Ferrostatin1_3uM_T55Breast cancer cells 1 µM RSL3 + 3 µM Ferrostatin 2 h
SA354094210309_MDA_Timecourse_RSL3_n3_24h_RSL3_1uM_35Breast cancer cells 1 µM RSL3 24 h
SA354095210309_MDA_Timecourse_RSL3_n2_24h_RSL3_1uM_23Breast cancer cells 1 µM RSL3 24 h
SA354096210309_MDA_Timecourse_RSL3_n1_24h_RSL3_1uM_11Breast cancer cells 1 µM RSL3 24 h
SA354088210324_Rescue_Gust_compounds_2h_n2_RSL3_1uM_T54Breast cancer cells 1 µM RSL3 2 h
SA354089210324_Rescue_Gust_compounds_2h_n3_RSL3_1uM_T66Breast cancer cells 1 µM RSL3 2 h
SA354090210309_MDA_Timecourse_RSL3_n3_2h_RSL3_1uM_26Breast cancer cells 1 µM RSL3 2 h
SA354091210309_MDA_Timecourse_RSL3_n1_2h_RSL3_1uM_2Breast cancer cells 1 µM RSL3 2 h
SA354092210324_Rescue_Gust_compounds_2h_n1_RSL3_1uM_T42Breast cancer cells 1 µM RSL3 2 h
SA354093210309_MDA_Timecourse_RSL3_n2_2h_RSL3_1uM_14Breast cancer cells 1 µM RSL3 2 h
SA354097210309_MDA_Timecourse_RSL3_n3_4h_RSL3_1uM_29Breast cancer cells 1 µM RSL3 4 h
SA354098210309_MDA_Timecourse_RSL3_n1_4h_RSL3_1uM_5Breast cancer cells 1 µM RSL3 4 h
SA354099210309_MDA_Timecourse_RSL3_n2_4h_RSL3_1uM_17Breast cancer cells 1 µM RSL3 4 h
SA354100210309_MDA_Timecourse_RSL3_n3_6h_RSL3_1uM_32Breast cancer cells 1 µM RSL3 6 h
SA354101210309_MDA_Timecourse_RSL3_n1_6h_RSL3_1uM_8Breast cancer cells 1 µM RSL3 6 h
SA354102210309_MDA_Timecourse_RSL3_n2_6h_RSL3_1uM_20Breast cancer cells 1 µM RSL3 6 h
SA354124210324_Rescue_Gust_compounds_2h_n1_Ti41_3uM_T45Breast cancer cells 3 µM Comp. 1 2 h
SA354125210324_Rescue_Gust_compounds_2h_n3_Ti41_3uM_T69Breast cancer cells 3 µM Comp. 1 2 h
SA354126210324_Rescue_Gust_compounds_2h_n2_Ti41_3uM_T57Breast cancer cells 3 µM Comp. 1 2 h
SA354127210324_Rescue_Gust_compounds_2h_n1_Ti41_F_3uM_T48Breast cancer cells 3 µM Comp. 2 2 h
SA354128210324_Rescue_Gust_compounds_2h_n3_Ti41_F_3uM_T72Breast cancer cells 3 µM Comp. 2 2 h
SA354129210324_Rescue_Gust_compounds_2h_n2_Ti41_F_3uM_T60Breast cancer cells 3 µM Comp. 2 2 h
SA354130210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_3uM_T51Breast cancer cells 3 µM Comp. 3 2 h
SA354131210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_3uM_T75Breast cancer cells 3 µM Comp. 3 2 h
SA354132210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_3uM_T63Breast cancer cells 3 µM Comp. 3 2 h
SA354139210309_MDA_Timecourse_RSL3_n3_24h_DMSO_34Breast cancer cells DMSO 24 h
SA354140210309_MDA_Timecourse_RSL3_n2_24h_DMSO_22Breast cancer cells DMSO 24 h
SA354141210309_MDA_Timecourse_RSL3_n1_24h_DMSO_10Breast cancer cells DMSO 24 h
SA354133210324_Rescue_Gust_compounds_2h_n3_DMSO_T65Breast cancer cells DMSO 2 h
SA354134210309_MDA_Timecourse_RSL3_n1_2h_DMSO_1Breast cancer cells DMSO 2 h
SA354135210324_Rescue_Gust_compounds_2h_n2_DMSO_T53Breast cancer cells DMSO 2 h
SA354136210309_MDA_Timecourse_RSL3_n3_2h_DMSO_25Breast cancer cells DMSO 2 h
SA354137210309_MDA_Timecourse_RSL3_n2_2h_DMSO_13Breast cancer cells DMSO 2 h
SA354138210324_Rescue_Gust_compounds_2h_n1_DMSO_T41Breast cancer cells DMSO 2 h
SA354142210309_MDA_Timecourse_RSL3_n3_4h_DMSO_28Breast cancer cells DMSO 4 h
SA354143210309_MDA_Timecourse_RSL3_n2_4h_DMSO_16Breast cancer cells DMSO 4 h
SA354144210309_MDA_Timecourse_RSL3_n1_4h_DMSO_4Breast cancer cells DMSO 4 h
SA354145210309_MDA_Timecourse_RSL3_n3_6h_DMSO_31Breast cancer cells DMSO 6 h
SA354146210309_MDA_Timecourse_RSL3_n2_6h_DMSO_19Breast cancer cells DMSO 6 h
SA354147210309_MDA_Timecourse_RSL3_n1_6h_DMSO_7Breast cancer cells DMSO 6 h
Showing results 1 to 72 of 72

Collection:

Collection ID:CO003373
Collection Summary:Cultured cells were washed, trypsinized, counted and flash-frozen in liquid N2 and stored at -80°C.
Sample Type:Breast cancer cells
Storage Conditions:-80℃

Treatment:

Treatment ID:TR003389
Treatment Summary:Treatment of breast cancer cells (MDA-MB-231 cells) for the analysis of PE and PC: Human MDA-MB-231 breast cancer cells were treated with vehicle (DMSO) or RSL3 (1 or 10 µM) with or without ferrostatin-1 (3 µM) for 2 h, 4 h, 6 h, or 24 h or with SCs (1, 3, and 10 µM) for 2 h at 37°C and 5% CO2. Cells were harvested, washed with PBS pH 7.4, snap-frozen, and stored at -80°C.

Sample Preparation:

Sampleprep ID:SP003387
Sampleprep Summary:Phospholipids were extracted from cell pellets by successive addition of PBS pH 7.4, methanol, chloroform, and saline to a final ratio of 14:34:35:17. Evaporation of the organic layer yielded a lipid film that was dissolved in methanol and subjected to UPLC-MS/MS.
Extract Storage:-80℃

Combined analysis:

Analysis ID AN005344
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity H-Class
Column Waters ACQUITY UPLC BEH C8 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTRAP
MS instrument name ABI Sciex 6500+
Ion Mode NEGATIVE
Units relative intensities

Chromatography:

Chromatography ID:CH004046
Chromatography Summary:Chromatographic separation of phospholipids was carried out on an Acquity BEH C8 column (1.7 μm, 130 Å, 2.1×100 mm, Waters, Milford, MA) using an ExionLC UHPLC system.
Instrument Name:Waters Acquity H-Class
Column Name:Waters ACQUITY UPLC BEH C8 (100 x 2.1mm,1.7um)
Column Temperature:45°C
Flow Gradient:The gradient was ramped from 75 to 85% B over 5 min and further increased to 100% B within 2 min, followed by isocratic elution for another 2 min.
Flow Rate:0.75 mL/min
Solvent A:90% Water, 10% Acetonitrile; 2 mM ammonium acetate
Solvent B:5% Water, 95% Acetonitrile; 2 mM ammonium acetate
Chromatography Type:Reversed phase

MS:

MS ID:MS005074
Analysis ID:AN005344
Instrument Name:ABI Sciex 6500+
Instrument Type:QTRAP
MS Type:ESI
MS Comments:Targeted MRM with pre-optimized settings and subsequent automated integration of selected signals using Analyst 1.6.3 or Analyst 1.7.1 (Sciex). Relative intensities (indicating the proportion of lipids) were obtained by summing all signals analyzed within the subgroup (e.g., PE) and expressing the individual signals of lipid species or lipid subfractions as a percentage of this sum (= 100%).
Ion Mode:NEGATIVE
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