Enucleation: a possible mechanism of cancer cell death

Abstract

There are few major morphologies of cell death that have been described so far: apoptosis (type I), cell death associated with autophagy (type II), necrosis (type III) and anchorage-dependent mechanisms—anoikis. Here, we show for the first time a possibly novel mechanism inducing tumour cell death under in vitro conditions—enucleation. We pursued the influence of colloidal suspensions of Fe3O4 nanoparticles on tumour cell lines (SK-BR-3 and MCF-7 breast cancer cell lines) grown according to standard cell culture protocols. Magnetite nanoparticles were prepared by combustion synthesis and double layer coated with oleic acid. Scanning and transmission electron microscopy revealed that tumour cells developed a network of intracytoplasmic stress fibres, which induce extrusion of nuclei, and enucleated cells die. Normal adult mesenchymal stem cells, used as control, did not exhibit the same behaviour. Intact nuclei were found in culture supernatant of tumour cells, and were visualized by immunofluorescence. Enucleation as a potential mechanism of tumour cell death might open new horizons in cancer biology research and development of therapeutic agents capable of exploiting this behaviour.

Magnetic Nanoparticles (MNPs) Influence on SK-BR3 Breast Cancer Cell Line - in vitro Study

“…1C). The influence of combustion-obtained MNPs was previously discussed, and the loss of nuclei was described as enucleation [8].…”

The natural adaptive evolution of cancer: The metastatic ability of cancer cells

“…We hypothesized that under particular biochemical and psychical circumstances, cancer cell nuclear expulsion [30] coupled with macrophage fusion, which results in a fusion hybrid, is a possible mechanism of survival and metastasis capability of cancer cells.…”

“…The remaining outstanding enigmas pertain to the ability of a cancer cell or part of it, for example, the nucleus [30], to survive the processes of migration to another part of the body. Regarding this, CTCs have been scientifically known to have a mean diameter of approximately 25 µm and are mostly adherent to platelets (CTCs with aggregated platelets have an even larger diameter), thus hindering their passage through capillary valves, which are approximately 8 µm in diameter.…”

Preclinical Aspects on Magnetic Iron Oxide Nanoparticles and Their Interventions as Anticancer Agents: Enucleation, Apoptosis and Other Mechanism

“…A novel proposed mechanism for M-IONPs-induced cell death is enucleation described by Paunescu and coworkers, process observed after exposure of breast cancer cells (MCF-7) and human melanoma (SK-BR-3) to magnetic iron oxide nanoparticles obtained by combustion synthesis [106]. The enucleation phenomena is well described for erythroid terminal differentiation process and there is also used a term in the literature "enucleation sign" that is specific for enhanced computed tomographic images of the ruptured hepatocellular carcinoma.…”

“…The definition for this term is "the separation of tumor content with intraperitoneal rupture into the perihepatic space, which is seen as low attenuating lesion from peripheral enhancing rim on arterial phase imaging" [107]. The process observed by Paunescu et al was described as a non-physiological process and it was unrelated with the process described for erythroblast enucleation [106].…”