Aim: The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.
Main methods: The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways.
Key findings: MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells.
Significance: This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.
Keywords: 2-Methoxy-1,4-naphthoquinone (MNQ); Lung adenocarcinoma; Mitogen-activated protein kinase (MAPK); Reactive oxygen species (ROS).
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