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Beclin-1, LC3, caspase 3, silica nanoparticles, autophagy, apoptosis, human lung adenocarcinoma A549, ultra-structure analysis
Metal nanoparticles are potential agents that cause autophagy dysfunction. Silica nanoparticles (SiNPs) can induce autophagy. Hence, the goal of this study is to provide evidence of the ability of silica nanoparticles to induce autophagy-associated apoptosis. In this report, silica nanoparticles exhibited dose-dependent cytotoxicity in lung adenocarcinoma A549 cells. Multiple assays verified that the activity of silica nanoparticles to induce autophagy blocked the autophagic flux at 50μg/ml. Furthermore, SiNPs impaired lysosomal function by damaging lysosomal ultrastructures. The results revealed that silica nanoparticles activated apoptosis with 26.39% and arrested the cell cycle at S phase due to an increase in the percentage of cells at S with 10 percent as compared with the negative control. Furthermore, the caspase 3 assay indicated that the activity of silica nanoparticles to induce apoptosis throughout the caspase cascades was evaluated by inducing oxidative stress (MDA), which is considered a lipid peroxidation marker. The rt-Pcr results showed down-regulation of LC3, while beclin 1 showed overexpression. Both LC3 and beclin 1 are autophagic genes that regulate the autophagy process. The immunohistochemistry showed a weaker Beclin 1. Transmission electron microscopy showed autophagosomes that are considered the benchmark for autophagy studies; the number of double-membrane autophagosomes and single-membrane autolysosomes was obviously observed in SiNP-treated A549. The current study provides a potential mechanism for autophagy dysfunction induced by silica nanoparticles in A549 cells.
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