Differences in intracellular mobile zinc levels affect susceptibility to plasma-activated medium-induced cytotoxicity. (4th March 2017)

• Record Type: Journal Article
• Authors: Hara, Hirokazu; Sueyoshi, Sayako; Taniguchi, Miko; Kamiya, Tetsuro; Adachi, Tetsuo
• Is Part Of: Free radical research. Volume 51:Number 3(2017:Mar.)
• Page Start: 306
• Page End: 315
• Publication Date: 2017-03-04
• Subjects: Plasma-activated medium -- non-thermal plasma -- zinc -- ROS -- mitochondria; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2017.1309527
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: There is growing evidence that plasma-activated medium (PAM), which is prepared by non-thermal plasma (NTP) irradiation of cell-free medium, is a beneficial tool for cancer therapy. PAM has been reported to preferentially kill cancer cells; however, its mechanism is not fully understood. Since PAM contains reactive oxygen species (ROS) and reactive nitrogen species, the anti-cancer effects of PAM are thought to be attributed to oxidative stress induced by these reactive molecules. Oxidative stress has been shown to release zinc (Zn 2+ ) from intracellular Zn 2+ stores and provoke Zn 2+ -dependent cell death. We have previously demonstrated that intracellular free Zn 2+ plays a critical role in PAM-induced cell death in human neuroblastoma SH-SY5Y cells. In this study, we found that normal human fibroblasts were less susceptible to PAM cytotoxicity compared with SH-SY5Y cells. PAM decreased intracellular NAD + levels in both cells, whereas the depletion of ATP and mitochondrial ROS generation was hardly observed in fibroblasts. Intracellular mobile Zn 2+ contents of fibroblasts were lower than those of SH-SY5Y cells. PAM suppressed the activity of aconitase, which is a tricarboxylic acid cycle enzyme, only in SH-SY5Y cells, and N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a Zn 2+ chelator, counteracted the suppression. The combination treatment with PAM and Zn 2+ augmented PAM-induced ATP depletion, mitochondrial ROS generation, and cytotoxicity in fibroblasts. These findings suggest the possibility that cells with high intracellular mobile Zn 2+ are susceptible to PAM cytotoxicity. Therefore, we concluded that the differences in mobile Zn 2+ levels affect PAM-induced cellular responses.