Analysis of redox processes from in silico perspective in colorectal cancer cell line

Oxidation and reduction processes (redox) are essential for the proper functioning of healthy cells, where the environment creates a prooxidant-antioxidant balance. Disturbance of this balance, such as the increase of oxidative stress due to the reduction of antioxidant systems, leads to pathological changes in cells and disease occurrence, including cancer. Glutathione (GSH) is an antioxidant capable of preventing damage to cellular components caused by reactive oxygen species (ROS), such as superoxide anion radical, hydroxyl radical and hydrogen peroxide. GSH protects the cells by neutralising ROS in a way that it changes form from reduced (GSH) to an oxidised state (GSSG). The final maintenance of the ratio between GSH-GSSG is a key factor in the defence of the cell from exposure to oxidative stress and oxidative damage. Colon cancer cells (HCT-116) with disrupted balance of prooxidative-antioxidative systems can be treated with noble metals to recover the environment of healthy tissues. In this research, two types of gold complexes were applied to study in vitro the disruption of the redox balance in colorectal cancer. In silico models were developed in the first phase to replicate experimental observations and provide a good matching of the results (validation). In the second phase in silico models were used to predict temporal responses, by creating a fitting curve, and to perform sensitivity analysis to highlight the influence of each component in the determined molecular mechanism of oxygen reactions, including the antioxidant enzymes’ role. Estimation of GSH-GSSG ratios in time was based upon the implementation of the bi-bi mechanism for enzymes. The mathematical model was created and solved in Matlab commercial software. The responses were collected for cases when gold complexes were not applied (control group) and when different concentrations of gold complexes were applied during the first 72h. Used concentrations of gold complexes were 0.1, 1, 10 and 50 [μM]. Calculated errors revealed that the range of predicted and experimental values have the same order of magnitude. Cytotoxicity results revealed the significant influence of one gold complex, especially at a concentration of 10 μM and higher, causing a higher production of free radicals and cytotoxic effect on the cancer cell line, which is confirmed by in silico results as well.