Cold atmospheric plasma (CAP) can induce cancer cell death. The majority of gene regulation studies have been biased towards reactive oxygen species (ROS) among the physicochemical components of CAP. The current study aimed to systemically determine the distribution of target genes regulated by the ROS and non-ROS constituents of CAP. Genome-wide expression data from a public database, which were obtained after treating U937 leukemia and SK-mel-147 melanoma cells with CAP or H2O2, were analyzed, and gene sets regulated by either or both of them were identified. The results showed 252 and 762 genes in H2O2-treated U937 and SK-mel-147 cells, respectively, and 112 and 843 genes in CAP-treated U937 and SK-mel-147 cells, respectively, with expression changes higher than two-fold. Notably, only four and two genes were regulated by H2O2 and CAP in common, respectively, indicating that non-ROS constituents were responsible for the regulation of the majority of CAP-regulated genes. Experiments using ROS and nitrogen oxide synthase (NOS) inhibitors demonstrated the ROS- and reactive nitrogen species (RNS)-independent regulation of PTGER3 and HSPA6 when U937 cancer cells were treated with CAP. Taken together, this study identified CAP-specific genes regulated by constituents other than ROS or RNS and could contribute to the annotation of the target genes of specific constituents in CAP.
Keywords: KEGG pathway; cold atmospheric plasma; leukemia cancer cells; reactive oxygen species; skin cancer cells.