Silver nanoparticles (AgNPs) are frequently detected in many convenience goods, such as cosmetics, that are applied directly to the skin. AgNPs accumulated in cells can modulate a wide range of molecular pathways, causing direct changes in cells. The aim of this study is to assess the capability of AgNPs to modulate the metastasis of breast cancer cells through the induction of epithelial-to-mesenchymal transition (EMT). The effect of the AgNPs on MCF-7 cells was investigated via the sulforhodamine B method, the wound healing test, generation of reactive oxygen species (ROS), the standard cytofluorimetric method of measuring the cell cycle, and the expression of EMT marker proteins and the MTA3 protein via Western blot. To fulfill the results, calcium flux and HDAC activity were measured. Additionally, mitochondrial membrane potential was measured to assess the direct impact of AgNPs on mitochondria. The results indicated that the MCF-7 cells are resistant to the cytotoxic effect of AgNPs and have higher mobility than the control cells. Treatment with AgNPs induced a generation of ROS; however, it did not affect the cell cycle but modulated the expression of EMT marker proteins and the MTA3 protein. Mitochondrial membrane potential and calcium flux were not altered; however, the AgNPs did modulate the total HDAC activity. The presented data support our hypothesis that AgNPs modulate the metastasis of MCF-7 cells through the EMT pathway. These results suggest that AgNPs, by inducing reactive oxygen species generation, alter the metabolism of breast cancer cells and trigger several pathways related to metastasis.
Keywords: MCF-7; breast cancer; epithelial–mesenchymal transition; estrogen; metastasis; silver nanoparticles.