Effects of Ferrocene and Ferrocenium on MCF-7 Breast Cancer Cells and Interconnection with Regulated Cell Death Pathways.

The effects of ferrocene () and ferrocenium () induced in triple negative human breast cancer MCF-7 cells were explored by immunofluorescence, flow cytometry, and transmission electron microscopy analysis. The different abilities of and to produce reactive oxygen species and induce oxidative stress were clearly observed by activating apoptosis and morphological changes after treatment, but also after tests performed on the model organism , particularly in the case of . The induction of ferroptosis, an iron-dependent form of regulated cell death driven by an overload of lipid peroxides in cellular membranes, occurred after 2 h of treatment with but not . However, the more stable showed its effects by activating necroptosis after a longer-lasting treatment. The differences observed in terms of cell death mechanisms and timing may be due to rapid interconversion between the two oxidative forms of internalized iron species (from Fe to Fe and vice versa). Potential limitations include the fact that iron metabolism and mitophagy have not been investigated. However, the ability of both and to trigger different and interregulated types of cell death makes them suitable to potentially overcome the shortcomings of traditional apoptosis-mediated anticancer therapies.