Iron stimulates plasma-activated medium-induced A549 cell injury.

Tetsuo Adachi,Hideko Nagasawa,Minori Horiba,Tasuku Hirayama,Tetsuro Kamiya,Hirokazu Hara,Saho Nonomura

doi:10.1038/srep20928

Tetsuo Adachi, Hideko Nagasawa + Show 5 more

Open Access

https://doi.org/10.1038/srep20928

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Journal: Scientific reports	Publication Date: Feb 11, 2016
Citations: 77	License type: CC BY 4.0

Affiliation: Gifu Pharmaceutical University

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 Ca2+. 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.

Highlights

Non-thermal atmospheric pressure plasma is applicable to living cells and has emerged as a novel technology for cancer therapy
Recent studies reported that plasma affected cancer cells directly, and by the indirect treatment of cells with previously prepared medium irradiated by plasma, termed plasma-activated medium (PAM)[4,5,6,7]
We recently reported that PAM functioned as a donor of reactive species, mainly H2O2, and induced apoptosis in the A549 human lung adenocarcinoma epithelial cell line and a few other cancer cell lines, and the addition of antioxidants, and iron chelators to PAM significantly attenuated reductions in A549 cells viability[10]

Summary

Introduction

Non-thermal atmospheric pressure plasma is applicable to living cells and has emerged as a novel technology for cancer therapy. Its radiation has been shown to generate some short- and long-lived molecules such as reactive oxygen and nitrogen species (RONS) mainly from oxygen and nitrogen in atmospheric air or solution[2]. Recent studies reported that plasma affected cancer cells directly, and by the indirect treatment of cells with previously prepared medium irradiated by plasma, termed plasma-activated medium (PAM)[4,5,6,7]. We recently reported that PAM functioned as a donor of reactive species, mainly H2O2, and induced apoptosis in the A549 human lung adenocarcinoma epithelial cell line and a few other cancer cell lines, and the addition of antioxidants, and iron chelators to PAM significantly attenuated reductions in A549 cells viability[10]. The aims of the present study were to demonstrate the contribution of iron to the amplification of PAM’s inhibitory effects on A549 cell survival and to elucidate the signaling mechanism responsible for cell death involving intracellular iron

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