Abstract
The therapeutic potential of nonthermal plasma for cancer treatment has been reported recently. The heterogeneity of cancer cells need to be addressed to design effective anticancer treatments. Here, we show that treatment with nonthermal atmospheric-pressure plasma dissolved in a liquid (liquid plasma) induces oxidative stress in heterogeneous populations of cancer cells and ultimately kills these cells via apoptosis, regardless of genetic status, e.g., mutations in p53 and other DNA-damage-response genes. We found that liquid plasma markedly increased the concentration of intracellular and mitochondrial reactive oxygen species (ROS), reflecting an influx from the extracellular milieu. Liquid plasma contributed to mitochondrial accumulation of ROS and depolarization of mitochondrial membrane potential with consequent cell death. Healthy normal cells, however, were hardly affected by the liquid-plasma treatment. The antioxidant N-acetylcysteine blocked liquid-plasma-induced cell death. A knockdown of CuZn-superoxide dismutase or Mn-SOD enhanced the plasma-induced cell death, whereas expression of exogenous CuZn-SOD, Mn-SOD, or catalase blocked the cell death. These results suggest that the mitochondrial dysfunction mediated by ROS production is a key contributor to liquid-plasma-induced apoptotic cell death, regardless of genetic variation. Thus, liquid plasma may have clinical applications, e.g., the development of therapeutic strategies and prevention of disease progression despite tumor heterogeneity.
Highlights
In a mechanistic extension of that study, we showed that nonthermal plasma generates various radicals, including ROS and/or reactive nitrogen species (RNS), causing mitochondrial dysfunction by disrupting mitochondrial membrane potential and ROS accumulation and thereby leading to death of the cancer cell via apoptosis[17,19]
To overcome the problem of limited penetrance of plasma, we examined the anticancer effects of nonthermal air plasma dissolved in a liquid
We first prepared liquid plasma (Fig. 1) by means of a microplasma jet system operated at atmospheric pressure[17,18,19,21] (Fig. 1A) that yielded the optical emission spectra (OES) associated with ROS or RNS (Fig. 1B)
Summary
In a mechanistic extension of that study, we showed that nonthermal plasma generates various radicals, including ROS and/or reactive nitrogen species (RNS), causing mitochondrial dysfunction by disrupting mitochondrial membrane potential and ROS accumulation and thereby leading to death of the cancer cell via apoptosis[17,19]. These effects of nonthermal-plasma-induced mitochondrial dysfunction prompted us to evaluate the suitability of plasma as a treatment option that can solve the problem of tumor heterogeneity. Our results suggest that research on plasma medicine may lead to the development of a novel anticancer treatment that is selectively cytotoxic to tumor cells (by targeting mitochondria) and is effective despite genetic heterogeneity within and between tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
