Summary of Study ST003261
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
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.
Study ID | ST003261 |
Study Title | Exploration of RSL3 or Chlorido[N,N’-disalicylidene-1,2-phenylenediamine]iron(III) complex-induced changes in the phospholipid oxidation of MDA-MB-231 breast cancer cells |
Study Summary | Chlorido[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 oxidized phospholipid profile by targeted lipidomics. SCs induce extensive (hydroper)oxidation of arachidonic acid and adrenic acid in membrane phospholipids, particularly phosphatidylethanolamines (PE) and phosphatidylinositols (PC). In this process, SCs have demonstrated superior efficacy compared to the GPX4 inhibitor RSL3, an established ferroptosis inducer. Please note that one sample set was measured three times with the same sample-ID, but with different methods (oxPE, oxPC, oxPI), therefore each sub-class has their own raw-data file marked by their corresponding abbreviation (oxPE, oxPC, oxPI; e.g. "210309_MDA_Timecourse_RSL3_oxPE_dil_UD_Std_1ul_SFT.wiff", "210324_Rescue_Gust_compounds_oxPE_dil_UD_std_1ul_SFT.wiff", "210309_MDA_Timecourse_RSL3_oxPC_dil_UD_Std_1ul_SFT.wiff", "210324_Rescue_Gust_compounds_oxPC_dil_UD_std_1ul_SFT.wiff" or "210324_Rescue_Gust_compounds_oxPI_dil_UD_std_1ul_SFT.wiff", ). |
Institute | University of Innsbruck |
Last Name | Koeberle |
First Name | Andreas |
Address | Mitterweg 24, Innsbruck, Tyrol, 6020, Austria |
Andreas.Koeberle@uibk.ac.at | |
Phone | +43 512 507 57903 |
Submit Date | 2024-06-12 |
Raw Data Available | Yes |
Raw Data File Type(s) | wiff |
Analysis Type Detail | LC-MS |
Release Date | 2024-06-27 |
Release Version | 1 |
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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 |