title: Iron stimulates plasma-activated medium-induced A549 cell injury.
abstract: Non-thermal atmospheric pressure plasma is applicable to living cells and has emerged as a novel technology for cancer therapy. Plasma has recently been shown to affect cells not only by direct irradiation, but also by indirect treatments with previously prepared plasma-activated medium (PAM). Iron is an indispensable element but is also potentially toxic because it generates the hydroxyl radical (•OH) in the presence of hydrogen peroxide (H2O2) via the Fenton reaction. The aim of the present study was to demonstrate the contribution of iron to PAM-induced A549 adenocarcinoma cell apoptosis. We detected the generation of •OH and elevation of intracellular ferrous ions in PAM-treated cells and found that they were inhibited by iron chelator. The elevations observed in ferrous ions may have been due to their release from the intracellular iron store, ferritin. Hydroxyl radical-induced DNA injury was followed by the activation of poly(ADP-ribose) polymerase-1, depletion of NAD(+) and ATP, and elevations in intracellular Ca(2+). The sensitivities of normal cells such as smooth muscle cells and keratinocytes to PAM were less than that of A549 cells. These results demonstrated that H2O2 in PAM and/or •OH generated in the presence of iron ions disturbed the mitochondrial-nuclear network in cancer cells.
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Tetsuo
authors: T
authors: Adachi
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Saho
authors: S
authors: Nonomura
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Minori
authors: M
authors: Horiba
authors: Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Tasuku
authors: T
authors: Hirayama
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Tetsuro
authors: T
authors: Kamiya
authors: Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Hideko
authors: H
authors: Nagasawa
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors: Hirokazu
authors: H
authors: Hara
mesh_terms: D000072283:A549 Cells; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004789:Enzyme Activation / Q000187:drug effects; D005293:Ferritins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D009928:Organ Specificity; D010084:Oxidation-Reduction; D058626:Plasma Gases / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D058626:Plasma Gases; D009243:NAD; D017665:Hydroxyl Radical; D000255:Adenosine Triphosphate; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D002118:Calcium