Stimulation of the immune system and apoptosis induction by new cobalt(III) H2salophen complexes in breast cancer mouse model and docking calculations.

Abstract

The increasing resistance of cancer drugs, especially in the treatment of breast cancer, underlines the urgent need for new and effective cancer drugs. Chemotherapeutic agents based on metal complexes are recognized as highly effective treatment options. The aim of this study is to synthesize a non-platinum chemotherapeutic agent with high efficacy and to investigate its therapeutic effect in mice with tumors. Novel transition metal complexes derived from Schiff base ligands (cobalt(III) H₂salophen complexes) were synthesized, characterized and optimized by quantum calculations based on DFT-D. MDA-MB231 and 4T1 cells were cultured and the scavenging and hemolysis activity, cytotoxic effect, migration and apoptosis were investigated. In addition, the therapeutic effects of the complex were investigated in mice with tumors. The interactions of the target macromolecules were investigated by molecular docking. The results showed that the complexes exhibited considerable cytotoxicity, apoptosis and migration inhibition against tumor cell lines and inhibition of tumor growth in mice, and greatly increased IFN-γ and TNF-α and reduced IL-4 and IL-1β. Data suggest that complex C treatment can enhance immune responses with a Th1 dominance by inducing the secretion of proinflammatory cytokines. Molecular docking experiments confirmed that complex C binds to the most stable state and induces apoptosis by interacting with the DNA minor groove. Our results suggest that complex C triggers apoptosis, leading to a lethal effect on malignant tumor cells, and has the potential to inhibit tumor growth through direct cytotoxic effects. It also stimulates the immune system and alters the cytokine profile.