International Journal of Radiation Research, cilt.22, sa.3, ss.739-748, 2024 (SCI-Expanded)
Background: Chloridazon belongs to the pyridazinone group of herbicides. Pyridazinone derivatives are known to have various pharmacological activities, including anti-cancer effects. Therefore, our study aimed to assess the cytotoxicity, apoptotic, anti-metastasis, and anti-angiogenesis effects of chloridazon-loaded alginate-chitosan nanocapsules on the 4T1 breast cancer cell line. Materials and Methods: The 4T1 cell line was cultured in RPMI 1640 media and treated with different concentrations of chloridazon-loaded alginate-chitosan nanocapsules. Cell viability was evaluated using the MTT assay, while cell vitality was assessed using the NR uptake assay. Apoptosis was induced and observed through acridine orange and propidium iodide staining. Furthermore, the expression levels of genes associated with metastasis (MMP-2 & MMP-9) and angiogenesis (VEGF-A) were analyzed using the RT-PCR technique. Results: The chloridazon-loaded nanocapsules displayed increased cytotoxicity on the 4T1 cell line in a dose-dependent manner. As the treatment dose increased, both cell viability and vitality decreased. The IC50 of the nanoformulation was measured as 74 μg/ml based on the dose-response curve. Additionally, the nanoformulation was found to induce apoptosis and decrease the expression levels of genes related to metastasis (MMP-2 & MMP-9) and angiogenesis (VEGF-A). Notably, the doses of 100 μg/ml and 160 μg/ml of the nanoformulation exhibited the most significant effects. Conclusion: Our findings reveal that the chloridazon-loaded alginate -chitosan nanocapsules have the potential to exert cytotoxic effects on the 4T1 breast cancer cell line.