Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma.
The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH-, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells.
Department of Life Science, Ajou University, Suwon, Korea.
Hak Jun
HJ
Ahn
Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
Kang Il
KI
Kim
Department of Life Science, Ajou University, Suwon, Korea.
Nguyen Ngoc
NN
Hoan
School of Medicine, Ajou University, Suwon, Korea.
Churl Ho
CH
Kim
Department of Life Science, Ajou University, Suwon, Korea.
Eunpyo
E
Moon
School of Medicine, Ajou University, Suwon, Korea.
Kyeong Sook
KS
Choi
Department of Electrical and Computer Engineering, Ajou University, Suwon, Korea.
Sang Sik
SS
Yang
Department of Life Science, Ajou University, Suwon, Korea.
Jong-Soo
JS
Lee
D000388:Air; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001274:Atmospheric Pressure; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D058626:Plasma Gases / Q000737:chemistry*; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013057:Spectrum Analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D058626:Plasma Gases; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases