# Low-Dose Oxidant Toxicity and Oxidative Stress in Human Papillary Thyroid Carcinoma Cells K1
###### Abstract
Lining up into an array of clinically approved redox-based therapy approaches, e.g., chemotherapeutic agents [4], photodynamic therapy [5], or radiotherapy [6], medical gas plasmas are of emerging interest in pre-clinical oncological research. Targeting the tumor redox balance, such plasmas feature a versatile mixture of reactive oxygen (ROS) and nitrogen species (RNS), causing lethal oxidative damage to cellular biomolecules [7]. Direct application of plasma-derived ROS/RNS is confined to the treatment of superficially growing, locally restricted neoplasms [8]. However, plasma-oxidized liquids can be considered concerning internal tumors with limited accessibility. Here, a carrier liquid is enriched with low-dose oxidants, applicable for intratumoral injections or lavage [9]. From a redox-chemistry point of view, only a few species are stable enough to persist in the liquid [10], and hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) is suggested to play a major role [11; 12; 13; 14; 15]. Anti-tumor effects of plasma-oxidized liquids are underlined by numerous studies, focusing on different tumor entities and a broad range of tumor models [16; 17; 18; 19; 20; 21]. However, knowledge of the applicability of such an approach in the treatment of thyroid cancer is scarce. Intriguingly, besides being important from a translational point of view, characterizing ROS-based therapy approaches in thyroid carcinoma is particularly interesting, as this neoplasm evolves in a highly oxidative environment. Throcytes are equipped with a large amount of dual oxygenase (DUOX) 2 and NADPH-oxidase (NOX) 4, important for H\({}_{2}\)O\({}_{2}\) generation required for thyroid hormone synthesis. As precise regulation of cellular H\({}_{2}\)O\({}_{2}\) levels is crucial to ensure proper thymocytes function and survival, cells are equipped with a powerful antioxidant defense system, representing an interesting target to study plasma-induced redox effects in tumor cells [22]. To this end, the present study explored metabolic activity, proliferation, viability, cellular oxidation, and the redox response of K1 cells, a lineage of papillary thyroid carcinoma carrying a heterozygous V600E mutation in the BRAF gene [23], after exposure to the plasma-oxidized medium. Cellular responses under mixed, plasma-derived ROS/RNS conditions were compared to H\({}_{2}\)O\({}_{2}\) and sodium nitroprusside, an RNS donor, alone (Figure 1a). Our findings will help to understand the behavior of PTC under different redox alterations and expand to evaluate the therapeutic use of reactive species in PTC. Figure 1: **Study scheme and treatment procedure. ****(a)** Study scheme: plasma-oxidized DMEM (oxDMEM), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)) and the reactive nitrogen species donor sodium nitroprusside (SNP) were investigated for their effects on metabolic activity, proliferation, viability and redox balance in a human papillary thyroid carcinoma cell line; (**b**) scheme of the generation of oxD-MEM; (**c**) representative image of the generation of ox DMEM. ROS = reactive oxygen species. slm = standard liters per minute.