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.

Mechanisms of a novel anticancer therapeutic strategy involving atmospheric pressure plasma-mediated apoptosis and DNA strand break formation

“…2a). Antioxidants such as N-acetyl cysteine (NAC), carboxy-PTIO (cPTIO), and sodium pyruvate (SP) were able to ablate depolarization of the mitochondrial membrane potential and impede apoptosis, suggesting that plasma-induced ROS/RNS themselves are a direct and sufficient cause of cell death, operating in a manner that mimicks natural pathways of apoptosis (Ahn et al 2014). Moreover, plasma has been developed as a potential approach for cancer therapy because of its selective efficacy toward cancer cells.…”

Plasma-activated medium induces A549 cell injury via a spiral apoptotic cascade involving the mitochondrial–nuclear network

“…These relatively short-lived RONS produced in media by plasma irradiation may be converted to other relatively long-lived species such as hydrogen peroxide (H 2 O 2 ), nitrate/nitrite (NO x ), and other uncertain species, which endow PAM with high and sustainable reactivity [13,16,17]. RONS are known to induce apoptosis via several signaling cascades including mitogen-activated protein kinase and phosphatidylinositol-3-kinase-Akt [8,18,19]. However, the mechanisms underlying the effects of PAM on cancer cells have not yet been elucidated in detail.…”

Cold Atmospheric Plasma Inhibits HIV-1 Replication in Macrophages by Targeting Both the Virus and the Cells

“…In total, 20% of cells on the plate received maximal treatment, 60% got intermediate dose, and 20% were not treated at all. The cold plasma jet system operated at atmospheric pressure can produce chemically active species, particularly oxygen and nitrogen atoms [14, 15]. To characterize the emission spectrum of our jet, we employed optical emission spectroscopy (OES) over a wide range of wavelengths from 200 nm to 900 nm with an optical emission spectroscope (SV 2100, K-MAC).…”