Effects of Ferrocene and Ferrocenium on MCF-7 Breast Cancer Cells and Interconnection with Regulated Cell Death Pathways. in Molecules (Basel, Switzerland) / Molecules. 2023 Sep 6;28(18):6469. doi: 10.3390/molecules28186469.
2023
ASL Vercelli
Tipo pubblicazione
Journal Article
Autori/Collaboratori (7)Vedi tutti...
Favaron C
Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Gabano E
Department of Sustainable Development and Ecological Transition, University of Piemonte Orientale, Piazza S. Eusebio 5, 13100 Vercelli, Italy.
Zanellato I
Department of Sciences and Technological Innovation, University of Piemonte Orientale, Viale Teresa Michel 11, 15121 Alessandria, Italy.
et alii...
Abstract
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 Fe(2+) to Fe(3+) 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.
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PMID : 37764244
DOI : 10.3390/molecules28186469
Keywords
Iron/metabolism; Apoptosis/physiology; Metallocenes/pharmacology; MCF-7 Cells; regulated cell death; oxidative stress; organoiron derivatives; Breast Neoplasms/drug therapy; Female; Humans; ferroptosis; Reactive Oxygen Species/metabolism;