Titanium Dioxide Nanoparticles Inhibits Entosis in the Human Breast Adenocarcinoma Cell Line

Abstract

TiO2 is widely used in industry and cosmetics and medicines production. In recent years, to achieve tumor-specific delivery of anticancer agents, TiO2 nanoparticles have been used in chemo/photodynamic therapy, which may cause local increase of the TiO2 concentration in tumors. The TiO2 nanoparticles can affect various processes in tumors. One of such process is entosis. During entosis one tumor cell invades another tumor cell. The aim of this work was to study the effect of TiO2 nanoparticles (anatase 25 nm and rutil/anatase 75 nm; 1, 10 and 100 µg/mL, 72 hours) on the entosis in the human breast adenocarcinoma cell line (MCF7). Cultivation of cells in the presence of nanoparticles lead to a slowdown in proliferation and reduced in the entosis number. These effects were dose-dependent. Elemental analysis (analytical electron microscopy) showed presence TiO2 nanoparticles in the cell vacuoles, in the cytosol and in the extracellular space. TiO2 nanoparticles (10 µg/mL) significantly disrupted adhesive junctions in entotic cells and in cell culture in general (immunocytochemistry staining). The anatase nanoparticles induced p53 translocation into the nucleus. Thus, the obtained data showed that the TiO2 nanoparticles inhibited entosis in MCF-7 cells by means of disrupting the adhesive junction formation and preventing cell invasion. However, failure of adhesive contacts can facilitate tumor metastasis.