Cold atmospheric plasma selectively induces toxicity of prostate cancer cells associated with oxidative stress

Cold atmospheric plasma (CAP) is an ionized gas generated at atmospheric pressure in which the temperature of heavy particles (ions, molecules, atoms) remains close to room temperature. CAP produces a complex mixture of reactive oxygen and nitrogen species (RONS). Recent studies have demonstrated its ability to induce cell death in various cancer cell lines, both in vitro and in vivo . Interestingly, non-tumoral cells appear to be relatively less affected by CAP treatments, this phenomenon is referred to as CAP selectivity. This study aimed to investigate the differential selectivity of a CAP jet generated by dielectric barrier discharge (DBD) in human prostate cells, comparing prostate cancer PC3 cells with non-tumoral RWPE-1 cells. Cells were exposed to a CAP treatment for 5–60 s and cell viability (MTS assay), plasma membrane integrity (Propidium iodide, PI staining), morphology (phase-contrast microscopy), intracellular ROS production (DHE staining), and antioxidant enzyme activities (SOD (superoxide dismutase), catalase, GPx (glutathione peroxidase)) were assessed 4 h and 24 h post-treatment. CAP exposure induced a time-dependent decrease in PC3 cell viability, with significant effect on viability observed at exposures ≥30 s, whereas RWPE-1 cells showed relative resistance. PI staining confirmed greater plasma membrane damage in PC3 compared to RWPE-1 cells. Morphological alterations such as cell rounding and detachment were more pronounced in PC3 cells than RWPE-1. CAP markedly increased intracellular ROS levels in PC3 cells (up to 73% DHE-positive after 60 s), accompanied by SOD upregulation and reduced catalase and GPx activities. In contrast, RWPE-1 cells exhibited a less pronounced oxidative response and preserved antioxidant enzyme activities. In summary, these results demonstrate differential sensitivity to CAP treatment between prostate cancer cells and non-tumoral cells under the tested conditions, associated with alterations in cellular redox status. These findings suggest that DBD-generated CAP may represent a promising targeted therapeutic approach for prostate cancer treatment.