Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma.

Abstract

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.