title: Anti-cancer efficacy of nonthermal plasma dissolved in a liquid, liquid plasma in heterogeneous cancer cells.
abstract: The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity.
authors.affiliation: Department of Life Sciences, Ajou University, Suwon, Korea.
authors.forename: Ngoc Hoan
authors.initials: NH
authors.lastname: Nguyen
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Sang Sik
authors.initials: SS
authors.lastname: Yang
authors.affiliation: Ajou University School of Medicine, Suwon, Korea.
authors.forename: Kyeong Sook
authors.initials: KS
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, Ajou University, Suwon, Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001274:Atmospheric Pressure; D002374:Catalase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D058626:Plasma Gases / Q000737:chemistry* / Q000633:toxicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D058626:Plasma Gases; D034741:RNA, Small Interfering; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002374:Catalase; D013482:Superoxide Dismutase; D000111:Acetylcysteine