Tumor cell metabolism correlates with resistance to gas plasma treatment: The evaluation of three dogmas

Gas plasma is a partially ionized gas increasingly recognized for targeting cancer. Several hypotheses attempt to explain the link between plasma treatment and cytotoxicity in cancer cells, all focusing on cellular membranes that are the first to be exposed to plasma-generated reactive oxygen species (ROS). One proposes high levels of aquaporins, membrane transporters of water and hydrogen peroxide, to mark tumor cell line sensitivity to plasma treatment. A second focuses on membrane-expression of redox-related enzymes such as NADPH oxidases (NOX) that may modify or amplify the effects of plasma-derived ROS, fueling plasma-induced cancer cell death. Another hypothesis is that the decreased cholesterol content of tumor cell membranes sensitizes these to plasmamediated oxidation and subsequently, cytotoxicity. Screening 33 surface molecules in 36 tumor cell lines in correlation to their sensitivity to plasma treatment, the expression of aquaporins or NOX members could not explain the sensitivity but were rather associated with treatment resistance. Correlation with transporter or enzyme activity was not tested. Analysis of cholesterol content confirmed the proposed positive correlation with treatment resistance. Strikingly, the strongest correlation was found for baseline metabolic activity (Spearman r = 0.76). Altogether, these data suggest tumor cell metabolism as a novel testable hypothesis to explain cancer cell resistance to gas plasma treatment for further elucidating this innovative field?s chances and limitations in oncology.

Automated summary

This passage discusses the use of gas plasma for cancer treatment along with several hypotheses regarding the mechanisms behind its cytotoxic effects on cancer cells. The focus is on cellular membranes exposed to reactive oxygen species generated by plasma, with theories involving aquaporins, NOX enzymes, and cholesterol content. Research on various tumor cell lines found that baseline metabolic activity had the strongest correlation with treatment sensitivity, indicating a potential new hypothesis to explore tumor cell resistance to gas plasma treatment in the field of oncology.