title: Cold Atmospheric Plasma Treatment Induces Anti-Proliferative Effects in Prostate Cancer Cells by Redox and Apoptotic Signaling Pathways.
abstract: One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cellular proliferation and consecutive molecular response mechanisms in established prostate cancer (PC) cell lines. PC cells showed a significantly reduced cell growth following CAP treatment as a result of both an immediate increase of intracellular peroxide levels and through the induction of apoptosis indicated by annexin V assay, TUNEL assay, and the evaluation of changes in nuclear morphology. Notably, co-administration of N-acetylcysteine (NAC) completely neutralized CAP effects by NAC uptake and rapid conversion to glutathione (GSH). Vitamin C could not counteract the CAP induced effects on cell growth. In summary, relatively short treatments with CAP of 10 seconds were sufficient to induce a significant inhibition of cancer proliferation, as observed for the first time in urogenital cancer. Therefore, it is important to understand the mode of CAP related cell death and clarify and optimize CAP as cancer therapy. Increased levels of peroxides can alter redox-regulated signaling pathways and can lead to growth arrest and apoptosis. We assume that the general intracellular redox homeostasis, especially the levels of cellular GSH and peroxidases such as peroxiredoxins affect the outcome of the CAP treatment.
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Department of Trauma and Reconstructive Surgery, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Gümbel
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Hanschmann
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Mandelkow
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gelbrich
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.affiliation: Department of Trauma and Reconstructive Surgery, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Ekkernkamp
authors.affiliation: Department of Trauma and Reconstructive Surgery, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Sckell
authors.affiliation: Department of Hygiene and Environmental Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Kramer
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Burchardt
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Lillig
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008297:Male; D058626:Plasma Gases / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005609:Free Radicals; D058626:Plasma Gases