Anti-Cancer Effects of Neocuproine via Copper Chelation in A549 Lung Adenocarcinoma Cells

Abstract

Objective: Neocuproine, a dipyridyl derivative with high affinity for copper ions, was investigated for its effects on human lung adenocarcinoma A549 cells, a key model for lung cancer research. Copper ions play crucial roles in cellular functions, such as angiogenesis and oxidative stress regulation, and their dysregulation is linked to tumor progression. This study evaluated neocuproine’s capacity to inhibit A549 cell proliferation and induce apoptosis, with a focus on pro-inflammatory cytokines and oxidative stress markers. Materials and Methods: To assess the cytotoxic effects of neocuproine, A549 cells were treated with doses ranging from 0.1 to 1000 μM. After 24 hours of incubation, cell viability was assessed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, total antioxidant status (TAS), total oxidant status (TOS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: A reduction in cell viability was observed in a concentration-dependent manner, with notable cytotoxic effects particularly evident at 10 and 100 μM doses. The IC50 of neocuproine was calculated as 31.28 μM (p<0.001). Changes in TAS, TOS, IL-6, and TNF-α levels corroborated the cytotoxicity findings from the MTT assay. Conclusion: Neocuproine effectively inhibited the growth of A549 lung cancer cells. This cytotoxic effect was particularly pronounced at doses between 10 and 100 µM, and was mediated by increasing oxidative stress and modulating inflammatory responses. These findings suggest that neocuproine is a potential therapeutic candidate for lung cancer. Further research is needed to fully understand its effects on healthy cells and biological systems.

Keywords

• Antioxidant
• A549
• Lung Cancer
• Neocuproine
• Pro-inflammatory cytokines

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