Аннотация:The IC50 value is a commonly used parameter for characterization of the cytotoxic potency of vast majority of experimental and clinical compounds. However, the significance of this parameter is limited when the dependence of cell survival on drug concentration is non-linear. In particular, the complexity of cell death can be registered for combinations of chemically different compounds. We developed a set of mathematical tools for characterization of the differential cytotoxic efficacy of Reactive Oxygen Species (ROS) induced cell death upon reduction of copper (II). The combinations of Cu (II)-organic complexes or CuO nanoparticles with N-Acetyl Cysteine (NAC) (each agent alone at the non-toxic concentration) yielded the cytotoxicity that differed from very high to average and to negligibly low depending on the structure of the metal-containing compound. The developed mathematical tools allowed to rank Cu2+containing compounds according to the integral effect on survival of HCT116 colon carcinoma and K562 chronic myelogenous leukemia in combinations with NAC and to check its statistical significance. Based on the analysis of cell sensitization by NAC, the compounds were clustered as highly efficient, average and low efficient according to the reduction potential of Cu2+ cation in different atomic surroundings. The proposed mathematical approaches can be useful for characterization of cell death as a complement to traditional IC50 calculations or their replacement if the latter parameter is not applicable.
