Cold atmospheric plasma selectively induces G₀/G₁ cell cycle arrest and apoptosis in AR-independent prostate cancer cells

Purpose: Androgen receptor-independent prostate cancers do not respond to androgen blockage therapies and suffer from high recurrence rate. We aim to contribute to the establishment of novel therapeutic approaches against such malignancies. Materials and Methods: We examined whether and how cold atmospheric plasma delivers selectivity against AR-independent prostate cancers via cell viability, transwell assay, wound healing, cell apoptosis assay, flow cytometry, intracellular hydrogen peroxide determination assay, RONS scavenger assay and western blot using human normal epithelial prostatic cells PNT1A and AR-negative DU145 prostate cancer cells. Results: We show that cold atmospheric plasma could selectively halt cell proliferation and migration in androgen receptor-independent cells as a result of induced cell apoptosis and G0/G1 stage cell cycle arrest, and such outcomes were achieved through modulations on the MAPK and NF-kB pathways in response to physical plasma induced intracellular redox level. Conclusion: Our study reports cold atmospheric plasma induced reduction on the proliferation and migration of androgen receptor-independent prostate cancer cells that offers novel therapeutic insights on the treatment of such cancers, and provides the first evidence on physical plasma induced cell cycle G0/G1 stage arrest that warrants the exploration on the synergistic use of cold atmospheric plasma and drugs such as chemotherapies in eradicating such cancer cells.