Activity Alterations of 37 Tyrosine Kinase Inhibitors Upon kINPen Plasma Exposure in A549 Lung Cancer Cells

Abstract

Cold physical plasma shows promising preclinical results as an anticancer strategy. The technology generates a variety of reactive oxygen species (ROS) mediating gas plasma-induced effects in cells and tissues. On the cellular level, ROS can trigger oxidative stress-related responses. On the biomolecular level, ROS can introduce oxidative modifications, potentially leading to functional alterations. To better understand plasma treatment in oncology therapies, we treated tyrosine kinase inhibitors (TKIs) with plasma to investigate the efficacy upon oxidation as well as plasma pretreated A549 lung cancer cells before TKI treatment to investigate combination effects. Specifically, a library of 37 compounds was exposed to the atmospheric pressure argon plasma jet kINPen before being added to the cells. Most gas plasma-treated TKIs showed a significant decline in anticancer efficacy. The experimental compound NVP-AEW541 showed elevated tumor-toxic effects after exposure to gas plasma. In A549 cells pretreated with gas plasma, all TKIs but one showed additive toxicity. In summary, this first study on gas plasma treatment of TKIs and lung cancer cells in combination treatments revealed that direct gas plasma TKI treatment decreased the activity of most but not all compounds investigated, while gas plasma pretreated cells mostly showed additive toxicity in response to TKI exposure.