Iron(III)-salophene catalyzes redox cycles that induce phospholipid peroxidation and deplete cancer cells of ferroptosis-protecting cofactors.

ABSTRACT: Ferroptosis, a lipid peroxidation-driven cell death program kept in check by glutathione peroxidase 4 and endogenous redox cycles, promises access to novel strategies for treating therapy-resistant cancers. Chlorido [N,N'-disalicylidene-1,2-phenylenediamine]iron (III) complexes (SCs) have potent anti-cancer properties by inducing ferroptosis, apoptosis, or necroptosis through still poorly understood molecular mechanisms. Here, we show that SCs preferentially induce ferroptosis over other cell death programs in triple-negative breast cancer cells (LC₅₀ ≥ 0.07 μM) and are particularly effective against cell lines with acquired invasiveness, chemo- or radioresistance. Redox lipidomics reveals that initiation of cell death is associated with extensive (hydroper)oxidation of arachido

SUBMITTER: Su F 

PROVIDER: S-EPMC11263665 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature