  Cold atmospheric plasma (CAP) and plasma-treated liquids (PTLs) have recently
become a promising option for cancer treatment, but the underlying mechanisms
of the anti-cancer effect are still to a large extent unknown. Although
hydrogen peroxide has been recognized as the major anti-cancer agent of PTL and
may enable selectivity in a certain concentration regime, the co-existence of
nitrite can create a synergistic effect. We develop a mathematical model to
describe the key species and features of the cellular response towards PTL.
From the numerical solutions, we define a number of dependent variables, which
represent feasible measures to quantify cell susceptibility in terms of the
hydrogen peroxide membrane diffusion rate constant and the intracellular
catalase concentration. For each of these dependent variables, we investigate
the regimes of selective versus non-selective, and of synergistic versus
non-synergistic effect to evaluate their potential role as a measure of cell
susceptibility. Our results suggest that the maximal intracellular hydrogen
peroxide concentration, which in the selective regime is almost four times
greater for the most susceptible cells compared to the most resistant cells,
could be used to quantify the cell susceptibility towards exogenous hydrogen
peroxide. We believe our theoretical approach brings novelty to the field of
plasma oncology, and more broadly, to the field of redox biology, by proposing
new ways to quantify the selective and synergistic anti-cancer effect of PTL in
terms of inherent cell features.
