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
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 | ST003260 |
| Study Title | Exploration 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 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 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 |
| Department | Michael Popp Institute |
| 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 |
