The Impact of p53 Knockdown on the Expression of Antioxidant System Genes in Response to Platinum Complexes in Tumor and Non-Tumor Cells

Objective: Oxidative stress and antioxidant defense play crucial roles in carcinogenesis and anticancer therapy. The transcription factor p53, a central regulator of the cellular stress response, is involved in maintaining redox homeostasis; however, its role in regulating the antioxidant system (AOS) under genotoxic stress remains insufficiently studied. In this study, we investigated the influence of p53 on the expression of key AOS genes in both tumor and non-tumor cell lines. p53 induction was modeled by creating stress conditions that trigger the natural cellular response to damaging effects of platinum complexes. Methods: Stable clones with p53 gene knockdown were generated via RNA interference, allowing us to assess the role of p53 in regulating the AOS genes under study. Results: The results demonstrate that platinum complexes upregulate expression of the superoxide dismutase gene (SOD2) in a p53-dependent manner. Under the same conditions, p53 knockdown reduced SOD2 expression back to baseline levels, indicating that p53 is required for SOD2 induction during genotoxic stress. In contrast, catalase (CAT) gene expression varied depending on cell type and the nature of the stress stimulus. Conclusions: These findings highlight the critical role of p53 in modulating the antioxidant response under genotoxic stress and provide new insights into its functions in oxidative homeostasis and cancer therapy.