DOI: 10.26650/experimed.1895536 ISSN: 2667-5846

Experimental Evaluation of Malathion-Induced Cytotoxicity and SOD1 Gene Expression in Triple-Negative Breast Cancer Cells

Sevinç Akçay, Esma Demir, Betül Çilkolukısa, Beyza Nur Şanlı, Bayram Furkan Coşkun, Serap Yalçın Azarkan, Selin Özkan Kotiloğlu
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Objective: This study aimed to investigate the cytotoxic effects of the organophosphate pesticide malathion on triple-negative breast cancer (TNBC) cells and to examine its impact on superoxide dismutase 1 (SOD1) gene expression.Materials and Methods: Human MDA-MB-231 TNBC cells were treated with escalating concentrations of malathion. Cell viability was assessed using the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, and the half-maximal inhibitory concentration (IC₅₀) was determined. Wound healing and matrigel transwell invasion assays were performed to evaluate cell migration and invasive capacity, respectively. Following exposure to the IC₅₀ concentration for 24 and 48 hours, SOD1 mRNA levels were measured via real-time quantitative polymerase chain reaction (RT-qPCR). Molecular docking analyses were performed using AutoDock and SeamDock to assess interactions between malathion and the human SOD1 protein (PDB ID: 2NAM).Results: Malathion reduced cell viability in a dose-dependent manner, with an IC₅₀ value of 17.79 μM after 48 hours of exposure. Treatment at this concentration significantly reduced both migratory activity (p<0.001) and invasive capacity (p<0.05). SOD1 mRNA expression decreased after 24 hours of exposure (0.6-fold relative to controls) and showed partial recovery at 48 hours (0.9-fold relative to controls). However, the difference between the two treatment groups was not statistically significant (p>0.05). Molecular docking predicted a binding affinity of −6.9 kcal/mol and revealed the formation of six hydrogen bonds between malathion and SOD1.Conclusion: Malathion exerted cytotoxic effects and impaired migration and invasion in MDA-MB-231 TNBC cells under cytotoxic exposure conditions. Although molecular docking predicted a potential interaction between malathion and SOD1, malathion did not significantly alter SOD1 transcription under the conditions examined. These findings should be considered preliminary and hypothesis-generating rather than definitive mechanistic evidence, and they warrant further investigation to clarify the molecular mechanisms underlying malathion-induced cellular responses.

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