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

The effects of ferrocene (Fc) and ferrocenium (Fc) 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 Fc and Fc 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 D. discoideum, particularly in the case of Fc. 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 Fc but not Fc. However, the more stable Fc 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 Fe²⁺ to Fe³⁺ and vice versa). Potential limitations include the fact that iron metabolism and mitophagy have not been investigated. However, the ability of both Fc and Fc to trigger different and interregulated types of cell death makes them suitable to potentially overcome the shortcomings of traditional apoptosis-mediated anticancer therapies.