Epithelial–Mesenchymal Transition Increases the Susceptibility of Human A549 Cells to Nanosecond Pulsed Electric Fields

Nanosecond pulsed electric fields (nsPEFs) are ultrashort, high-intensity electrical pulses that have unique biological actions, including the formation of membrane nanopores and the efficient induction of cell death. nsPEFs are currently regarded as a promising modality for cancer therapy. During cancer progression, abnormal cells become more malignant through epithelial-mesenchymal transition (EMT). EMT is a biological process in which cells acquire mesenchymal traits and thereby increase their motility and invasiveness. Despite the importance of EMT in cancer progression, however, limited information is available on whether EMT modulates cellular responses to nsPEFs. In this study, we compared the responses of EMT and non-EMT human A549 cells to nsPEFs. We found that EMT induction rendered A549 cells more susceptible to nsPEFs as evidenced by decreased cell viability and increased nanopore formation upon nsPEF exposure. nsPEFs predominantly induced non-apoptotic cell death in EMT cells, and extracellular Ca²⁺ augmented the cytotoxicity of nsPEFs, suggesting involvement of nanopore-mediated Ca²⁺ influx in cytotoxicity. These findings reveal a novel feature of nsPEFs in targeting EMT cells, further supporting the unique biological actions of nsPEFs and their therapeutic potential for cancer.