title: Nonthermal plasma induces apoptosis in ATC cells: involvement of JNK and p38 MAPK-dependent ROS.
abstract: OBJECTIVE
  To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O₂) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells.
  
  
  METHODS
  NTP was generated in He alone or He plus O₂ blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma.
  
  
  RESULTS
  NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O₂ generated more O₂-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers.
  
  
  CONCLUSIONS
  NTP using He plus O₂ induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Sei Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Kang Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Sam
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
authors.forename: Sang Sik
authors.initials: SS
authors.lastname: Yang
authors.affiliation: PSM America Inc., Colorado Springs, CO, USA.
authors.forename: Keunho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology and Life Science, Ajou University, Suwon, Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Molecular Science and Technology and Life Science, Ajou University, Suwon, Korea.
authors.forename: Eunpyo
authors.initials: E
authors.lastname: Moon
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea. ostium@ajou.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D058626:Plasma Gases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013052:Spectrometry, X-Ray Emission; D065646:Thyroid Carcinoma, Anaplastic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D058626:Plasma Gases; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Nonthermal plasma; ROS; anaplastic thyroid cancer; apoptosis; helium; oxygen