Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions

Abstract

Non-thermal atmospheric pressure plasma has been widely used for preclinical studies in areas such as wound healing, blood coagulation, and cancer therapy. We previously developed plasma-activated medium (PAM) and plasma-activated Ringer’s lactate solutions (PAL) for cancer treatments. Many in vitro and in vivo experiments demonstrated that both PAM and PAL exhibit anti-tumor effects in several types of cancer cells such as ovarian, gastric, and pancreatic cancer cells as well as glioblastoma cells. However, interestingly, PAM induces more intracellular reactive oxygen species in glioblastoma cells than PAL. To investigate the differences in intracellular molecular mechanisms of the effects of PAM and PAL in glioblastoma cells, we measured gene expression levels of antioxidant genes such as CAT, SOD2, and GPX1. Microarray and quantitative real-time PCR analyses revealed that PAM elevated stress-inducible genes that induce apoptosis such as GADD45α signaling molecules. PAL suppressed genes downstream of the survival and proliferation signaling network such as YAP/TEAD signaling molecules. These data reveal that PAM and PAL induce apoptosis in glioblastoma cells by different intracellular molecular mechanisms.

Plasma-activated Ringer’s Lactate Solution Displays a Selective Cytotoxic Effect on Ovarian Cancer Cells

“…In this work, we produced a PA-RL through a multiwire plasma source, whose main innovative feature is its ability to work without the use of a technical gas, while allowing to treat 20 mL of liquid [28,[34][35][36]. Moreover, the source architecture we here propose can be easily scaled in order to produce volumes of activated solution higher than 20 mL.…”

“…Tanaka et al [26] first proposed the use of RL, whose simple composition (NaCl, KCl, CaCl 2 and lactate) makes it adoptable for the production of PAL, avoiding the possible influence of more organic medium components on its final biological effect [27]. It has been demonstrated that plasma-activated Ringer's Lactate solutions (PA-RL) exhibit an anti-tumor effect in lung, mammary, ovarian cancer cells as well as in glioblastoma in vitro [25,26,28], and in pancreatic and cervical cancer in vivo [26,29]. Several studies demonstrated that the effects of PA-RL may be ascribed to RONS, together with the activation of lactate [26,28].…”

“…It has been demonstrated that plasma-activated Ringer's Lactate solutions (PA-RL) exhibit an anti-tumor effect in lung, mammary, ovarian cancer cells as well as in glioblastoma in vitro [25,26,28], and in pancreatic and cervical cancer in vivo [26,29]. Several studies demonstrated that the effects of PA-RL may be ascribed to RONS, together with the activation of lactate [26,28]. All these results suggest that the use of PA-RL may represent a new potential therapeutic strategy for intraperitoneally disseminated cancers.…”

Nonthermal plasma as part of a novel strategy for vaccination

“…Although the mechanism of ICD induction associated with the different physical and chemical agents is not fully elucidated, a common theme is the induction of the oxidative and endoplasmic reticulum (ER) stress in exposed cells. [ 54,60,68–73 ] NTP has gained increasing attention over the last decade as being a highly controllable mechanism of delivering oxidative species to targets. The pioneering research by Lin et al in 2017 first described NTP as a tool to enhance immunogenicity of cancer cells through the induction of the ER stress.…”

The emerging role of cold atmospheric plasma in glioblastoma therapy

“…In a recent study, Tanaka et al [ 84 ] examined the differences in intracellular molecular mechanisms of the effects of PAM and plasma‐activated Ringer's lactate solution (PAL) in U251SP cells. They showed that PAM generates higher ROS in U251SP cells than PAL.…”