Anticancer Effects of Plasma-Treated Water Solutions from Clinically Approved Infusion Liquids Supplemented with Organic Molecules

Water solutions treated by cold atmospheric plasmas (CAPs)currently stand out in the field of cancer treatment as sources of exogenous blendsof reactive oxygen and nitrogen species (RONS). It is well known that the balanceof RONS inside both eukaryotic and prokaryotic cells is directly involved inphysiological as well as pathological pathways. Also, organic molecules includingphenols could exert promising anticancer effects, mostly attributed to their pro-oxidant ability in vitro and in vivo to generate RONS like O2−, H2O2, and amixture of potentially cytotoxic compounds. By our vision of combining theefficacy of plasma-produced RONS and the use of organic molecules, we could synergistically attack cancer cells; yet, so far, thiscombination, to the best of our knowledge, has been completely unexplored. In this study,L-tyrosine, an amino acid with a phenolicside chain, is added to a physiological solution, often used in clinical practice (SIII) to be exposed to plasma. The efficacy of the gasplasma-oxidized SIII solution, containing tyrosine, was evaluated on four cancer cell lines selected from among tumors with poorprognosis (SHSY-5Y, MCF-7, HT-29, and SW-480). The aim was to induce tumor toxicity and trigger apoptosis pathways. Theresults clearly indicate that the plasma-treated water solution (PTWS) reduced cell viability and oxygen uptake due to an increase inintracellular ROS levels and activation of apoptosis pathways in all investigated cancer cells, which may be related to the activation ofthe mitochondrial-mediated and p-JNK/caspase-3 signaling pathways. This research offers improved knowledge about thephysiological mechanisms underlying cancer treatment and a valid method to set up a prompt, adequate, and effective cancertreatment in the clinic.