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

Abstract

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.

Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities

“…CAP has been considered as a relatively mild promising onco-therapeutic approach with minimal adverse effects on healthy cells [ 133 ]. Moreover, CAP is known to cause controlled oxidative stress [ 45 , 132 ] that can alter many cell death programs such as cell cycle progression and apoptosis [ 134 ]. To aid in the understanding of CAP as a novel therapeutic, recent progress on its other applications is summarized in Supplementary Table S2 .…”

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination

“…Cold atmospheric plasma (CAP), composed of reactive oxygen and nitrogen species (RONS) and electric fields 6 - 9 , features multi-modal effects and can be generated via a range of device configurations, e.g., dielectric barrier discharge, plasma jet and plasma torch 10 . CAP has been used as diverse medical therapies 11 , 12 such as wound healing 13 , sterilization 14 , dental and dermatological treatments 15 , as well as showcased its safety and efficacy in resolving cancers of, e.g., breast 16 , prostate 17 , bladder 18 , brain 19 , 20 due to synergistic actions of its varied reactive components 21 , 22 . Specifically, these reactive species interact with cancer cell surface to selectively arrest cancer cells at various death states such as immunogenic cell death 23 , apoptosis 16 , cell cycle arrest 17 , and autophagy 24 by relaying a series of signalings.…”

“…CAP has been used as diverse medical therapies 11 , 12 such as wound healing 13 , sterilization 14 , dental and dermatological treatments 15 , as well as showcased its safety and efficacy in resolving cancers of, e.g., breast 16 , prostate 17 , bladder 18 , brain 19 , 20 due to synergistic actions of its varied reactive components 21 , 22 . Specifically, these reactive species interact with cancer cell surface to selectively arrest cancer cells at various death states such as immunogenic cell death 23 , apoptosis 16 , cell cycle arrest 17 , and autophagy 24 by relaying a series of signalings. Besides intensive preclinical efforts, the first clinical trial using CAP as an oncotherapy had been issued on 30 July 2019 and completed on 14 April 2021 in USA (NCT04267575) with success.…”

Cold Atmospheric Plasma Boosts Virus Multiplication via EGFR(Tyr1068) Phosphorylation-Mediated Control on Cell Mitophagy

“…Cold atmospheric plasma (CAP), belonging to the fourth state of matter, has been shown capable of preventing COVID-19 3 , deactivating viruses, removing pathogens such as bacteria and fungi 4 , and selectively killing cancer cells via inducing, e.g., cell cycle arrest 5 , senescence 6 , autophagy 7 , apoptosis 8 , ferroptosis 9 , 10 , ICD 11 , and necrosis 12 in a dose-dependent fashion 13 . It is composed of long-lived and short-lived reactive oxygen and nitrogen species, the chemical properties of which have been intensively studied 14 - 19 .…”