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
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Treatment time point
SA354103210324_Rescue_Gust_compounds_2h_n2_Ti41_10uM_T5810 µM Comp. 1 2 h
SA354104210324_Rescue_Gust_compounds_2h_n1_Ti41_10uM_T4610 µM Comp. 1 2 h
SA354105210324_Rescue_Gust_compounds_2h_n3_Ti41_10uM_T7010 µM Comp. 1 2 h
SA354106210324_Rescue_Gust_compounds_2h_n1_Ti41_F_10uM_T4910 µM Comp. 2 2 h
SA354107210324_Rescue_Gust_compounds_2h_n2_Ti41_F_10uM_T6110 µM Comp. 2 2 h
SA354108210324_Rescue_Gust_compounds_2h_n3_Ti41_F_10uM_T7310 µM Comp. 2 2 h
SA354109210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_10uM_T7610 µM Comp. 3 2 h
SA354110210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_10uM_T6410 µM Comp. 3 2 h
SA354111210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_10uM_T5210 µM Comp. 3 2 h
SA354115210309_MDA_Timecourse_RSL3_n2_24h_RSL3_10uM_2410 µM RSL3 24 h
SA354116210309_MDA_Timecourse_RSL3_n3_24h_RSL3_10uM_3610 µM RSL3 24 h
SA354117210309_MDA_Timecourse_RSL3_n1_24h_RSL3_10uM_1210 µM RSL3 24 h
SA354112210309_MDA_Timecourse_RSL3_n3_2h_RSL3_10uM_2710 µM RSL3 2 h
SA354113210309_MDA_Timecourse_RSL3_n2_2h_RSL3_10uM_1510 µM RSL3 2 h
SA354114210309_MDA_Timecourse_RSL3_n1_2h_RSL3_10uM_310 µM RSL3 2 h
SA354118210309_MDA_Timecourse_RSL3_n3_4h_RSL3_10uM_3010 µM RSL3 4 h
SA354119210309_MDA_Timecourse_RSL3_n2_4h_RSL3_10uM_1810 µM RSL3 4 h
SA354120210309_MDA_Timecourse_RSL3_n1_4h_RSL3_10uM_610 µM RSL3 4 h
SA354121210309_MDA_Timecourse_RSL3_n2_6h_RSL3_10uM_2110 µM RSL3 6 h
SA354122210309_MDA_Timecourse_RSL3_n3_6h_RSL3_10uM_3310 µM RSL3 6 h
SA354123210309_MDA_Timecourse_RSL3_n1_6h_RSL3_10uM_910 µM RSL3 6 h
SA354076210324_Rescue_Gust_compounds_2h_n1_Ti41_1uM_T441 µM Comp. 1 2 h
SA354077210324_Rescue_Gust_compounds_2h_n3_Ti41_1uM_T681 µM Comp. 1 2 h
SA354078210324_Rescue_Gust_compounds_2h_n2_Ti41_1uM_T561 µM Comp. 1 2 h
SA354079210324_Rescue_Gust_compounds_2h_n2_Ti41_F_1uM_T591 µM Comp. 2 2 h
SA354080210324_Rescue_Gust_compounds_2h_n3_Ti41_F_1uM_T711 µM Comp. 2 2 h
SA354081210324_Rescue_Gust_compounds_2h_n1_Ti41_F_1uM_T471 µM Comp. 2 2 h
SA354082210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_1uM_T621 µM Comp. 3 2 h
SA354083210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_1uM_T741 µM Comp. 3 2 h
SA354084210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_1uM_T501 µM Comp. 3 2 h
SA354085210324_Rescue_Gust_compounds_2h_n3_RSL3_1uM_Ferrostatin1_3uM_T671 µM RSL3 + 3 µM Ferrostatin 2 h
SA354086210324_Rescue_Gust_compounds_2h_n1_RSL3_1uM_Ferrostatin1_3uM_T431 µM RSL3 + 3 µM Ferrostatin 2 h
SA354087210324_Rescue_Gust_compounds_2h_n2_RSL3_1uM_Ferrostatin1_3uM_T551 µM RSL3 + 3 µM Ferrostatin 2 h
SA354094210309_MDA_Timecourse_RSL3_n3_24h_RSL3_1uM_351 µM RSL3 24 h
SA354095210309_MDA_Timecourse_RSL3_n2_24h_RSL3_1uM_231 µM RSL3 24 h
SA354096210309_MDA_Timecourse_RSL3_n1_24h_RSL3_1uM_111 µM RSL3 24 h
SA354088210324_Rescue_Gust_compounds_2h_n2_RSL3_1uM_T541 µM RSL3 2 h
SA354089210324_Rescue_Gust_compounds_2h_n3_RSL3_1uM_T661 µM RSL3 2 h
SA354090210309_MDA_Timecourse_RSL3_n3_2h_RSL3_1uM_261 µM RSL3 2 h
SA354091210309_MDA_Timecourse_RSL3_n1_2h_RSL3_1uM_21 µM RSL3 2 h
SA354092210324_Rescue_Gust_compounds_2h_n1_RSL3_1uM_T421 µM RSL3 2 h
SA354093210309_MDA_Timecourse_RSL3_n2_2h_RSL3_1uM_141 µM RSL3 2 h
SA354097210309_MDA_Timecourse_RSL3_n3_4h_RSL3_1uM_291 µM RSL3 4 h
SA354098210309_MDA_Timecourse_RSL3_n1_4h_RSL3_1uM_51 µM RSL3 4 h
SA354099210309_MDA_Timecourse_RSL3_n2_4h_RSL3_1uM_171 µM RSL3 4 h
SA354100210309_MDA_Timecourse_RSL3_n3_6h_RSL3_1uM_321 µM RSL3 6 h
SA354101210309_MDA_Timecourse_RSL3_n1_6h_RSL3_1uM_81 µM RSL3 6 h
SA354102210309_MDA_Timecourse_RSL3_n2_6h_RSL3_1uM_201 µM RSL3 6 h
SA354124210324_Rescue_Gust_compounds_2h_n1_Ti41_3uM_T453 µM Comp. 1 2 h
SA354125210324_Rescue_Gust_compounds_2h_n3_Ti41_3uM_T693 µM Comp. 1 2 h
SA354126210324_Rescue_Gust_compounds_2h_n2_Ti41_3uM_T573 µM Comp. 1 2 h
SA354127210324_Rescue_Gust_compounds_2h_n1_Ti41_F_3uM_T483 µM Comp. 2 2 h
SA354128210324_Rescue_Gust_compounds_2h_n3_Ti41_F_3uM_T723 µM Comp. 2 2 h
SA354129210324_Rescue_Gust_compounds_2h_n2_Ti41_F_3uM_T603 µM Comp. 2 2 h
SA354130210324_Rescue_Gust_compounds_2h_n1_Ti41_Cl_3uM_T513 µM Comp. 3 2 h
SA354131210324_Rescue_Gust_compounds_2h_n3_Ti41_Cl_3uM_T753 µM Comp. 3 2 h
SA354132210324_Rescue_Gust_compounds_2h_n2_Ti41_Cl_3uM_T633 µM Comp. 3 2 h
SA354139210309_MDA_Timecourse_RSL3_n3_24h_DMSO_34DMSO 24 h
SA354140210309_MDA_Timecourse_RSL3_n2_24h_DMSO_22DMSO 24 h
SA354141210309_MDA_Timecourse_RSL3_n1_24h_DMSO_10DMSO 24 h
SA354133210324_Rescue_Gust_compounds_2h_n3_DMSO_T65DMSO 2 h
SA354134210309_MDA_Timecourse_RSL3_n1_2h_DMSO_1DMSO 2 h
SA354135210324_Rescue_Gust_compounds_2h_n2_DMSO_T53DMSO 2 h
SA354136210309_MDA_Timecourse_RSL3_n3_2h_DMSO_25DMSO 2 h
SA354137210309_MDA_Timecourse_RSL3_n2_2h_DMSO_13DMSO 2 h
SA354138210324_Rescue_Gust_compounds_2h_n1_DMSO_T41DMSO 2 h
SA354142210309_MDA_Timecourse_RSL3_n3_4h_DMSO_28DMSO 4 h
SA354143210309_MDA_Timecourse_RSL3_n2_4h_DMSO_16DMSO 4 h
SA354144210309_MDA_Timecourse_RSL3_n1_4h_DMSO_4DMSO 4 h
SA354145210309_MDA_Timecourse_RSL3_n3_6h_DMSO_31DMSO 6 h
SA354146210309_MDA_Timecourse_RSL3_n2_6h_DMSO_19DMSO 6 h
SA354147210309_MDA_Timecourse_RSL3_n1_6h_DMSO_7DMSO 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℃

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

Analysis:

Analysis ID:AN005344
Analysis Type:MS
Chromatography ID:CH004046
Num Factors:22
Num Metabolites:78
Units:relative intensities
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