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Published on: December 15, 2014
Structural and morphological changes of breast cancer cells induced by iron(II) complexes
Janske Nel1, David Siniscalco2, Cécilia Hognon3
1Université de Lorraine, LIBio, F-54000, Nancy, France.
Abstract:
Metal-based complexes are well-established cancer chemotherapeutic drug candidates. Although our knowledge regarding their exact activity vs. toxicity profile is incomplete, changes in cell membrane biophysical properties and cytoskeletal structures have been implicated as part of the mechanism of action. Thus, in this work, we characterised the effects of iron(II)-based complexes on the structural and morphological properties of epithelial non-tumorigenic (MCF 10A) and tumorigenic (MDA-MB-231) breast cell lines using atomic force microscopy (AFM), flow cytometry and immunofluorescence microscopy. At 24 h of exposure, both the MCF 10A and MDA-MB-231 cells experienced a cell softening, and an increase in size followed by a re-stiffening at 96 h. In addition, the triple negative breast cancer cell line, MDA-MB-231, sustained a notable cytoskeletal and mitochondrial reorganization with increased actin stress fibers and cell-to-cell communication structures. An extensive all-atom molecular dynamic simulation suggests a possible direct and unassisted internalization of the metallodrug candidate, and confirmed that the cellular effects could not be ascribed to the simple physical interaction of the iron-based complexes with the biological membrane. These observations provide an insight into a link between the mechanisms of action of such iron-based complexes as anti-cancer treatment and cytoskeletal architecture.
Insights
Iron(II)-based complexes alter breast cell structure and mechanics, impacting cytoskeletal organization. These findings reveal a potential mechanism for iron-based metallodrugs in cancer therapy.
Area of Science:
- Biochemistry
- Cell Biology
- Materials Science
Background:
- Metal-based complexes are investigated as anticancer agents.
- Their precise mechanisms of action and toxicity profiles require further elucidation.
- Cellular biophysical property alterations are potential indicators of drug activity.
Purpose of the Study:
- To characterize the effects of iron(II)-based complexes on non-tumorigenic (MCF 10A) and tumorigenic (MDA-MB-231) breast cell lines.
- To investigate the impact on cell structure, morphology, and the cytoskeleton.
- To explore the internalization mechanism of the iron-based complexes.
Main Methods:
- Atomic force microscopy (AFM) for cell mechanical properties.
- Flow cytometry for cell analysis.
- Immunofluorescence microscopy for cytoskeletal and mitochondrial visualization.
- All-atom molecular dynamic simulations for internalization studies.
Main Results:
- Iron(II)-based complexes induced cell softening and size increase at 24 hours, followed by re-stiffening at 96 hours in both cell lines.
- MDA-MB-231 cells showed significant cytoskeletal and mitochondrial reorganization, including increased actin stress fibers.
- Molecular dynamics simulations suggested direct, unassisted internalization of the metallodrug candidate.
- Cellular effects were not due to simple physical interaction with the cell membrane.
Conclusions:
- Iron(II)-based complexes influence breast cell biophysical properties and cytoskeletal architecture.
- The observed cellular changes suggest a direct link between metallodrug mechanism of action and cytoskeletal dynamics.
- These findings offer insights into the potential of iron-based complexes as anticancer therapeutics.
