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. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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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℃

Combined analysis:

Analysis ID AN005344
Chromatography ID CH004046
MS ID MS005074
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 Triple quadrupole
MS instrument name ABI Sciex 6500+ QTrap
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+ QTrap
Instrument Type:Triple quadrupole
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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