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.
Highlights
Plasma is often referred to as the fourth state of matter in addition to solid, liquid, and gas
Because air plasma induced the generation of cellular ROS/ RNS (Figure 2) and mitochondrial ROS (Figure 5a) and the collapse of the mitochondrial transmembrane potential (Dym) [2], we examined whether ROS/RNS could be linked to the air plasma-induced mitochondrial dysfunction by treating HeLa cells with air plasma in the presence of the antioxidants NAC or cPTIO
By demonstrating that air plasma produces extracellular ROS and RNS and the generated extracellular ROS/RNS appear to translocate into the cells and induce intracellular and mitochondrial ROS/RNS production, this study, in conjunction with previous studies [2,33], explains what components and how air plasma induces cancer cell death
Summary
Plasma is often referred to as the fourth state of matter in addition to solid, liquid, and gas. Plasma is quite similar to gas in which a proportion of the particles is ionized and charged, some particles are electrically neutral, and some are chemically activated radicals. Plasma can be categorized as either ‘‘thermal (or hot) plasma’’ or ‘‘non-thermal (or cold) plasma.’’ Numerous techniques using plasma have been investigated and successfully implemented in certain industrial applications. Plasma applications have been employed in biological and medical sciences, including blood coagulation [1], cancer therapy [2], surface sterilization [3], and dental cavity treatment [4]. Increasing plasma translational research in cancer treatment may promise novel therapeutic effects. It is interesting that cold plasma generated at atmospheric pressure increases the feasibility of medical applications
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