Evaluation the cytotoxic effect of Fe3O4@Glu-Gingerol on lung adenocarcinoma cell line (A549) with biological mechanisms

评价Fe3O4@Glu-Gingerol对肺腺癌细胞株(A549)的细胞毒性作用及其生物学机制

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作者:Tabarek Abdulrazaq Alkinani, Fahimeh Abedini Bajgiran, Mohammad Rezaei, Ali Motamedi Maivan, Fatemeh Jafari Golrokh, Mona Bejarbaneh, Sara Rezaei Mojdehi, Sahar Gorji, Reza Ghasemian, Mohammad Dashtban Jalil Pustin Sarai, Fatemeh Akbari, Somayeh Dehghan, Fatemeh Mirzaee, Noor Hussein Abdulrahman, Al

Abstract

The use of nanotechnology products with supermagnetic properties for targeted delivery of drugs has gained attention recently. Due to the anticancer features of Gingerol, the major phenolic compound from Ginger, this study aims to prepare Fe3O4@Glucose-Gingerol nanoparticles (NPs) and investigate their anticancer potential in a lung adenocarcinoma cell line. The physical and chemical features of the nanoparticles were investigated by FT-IR, XRD, zeta potential, DLS, EDS mapping, VSM, and electron microscope imaging. Cytotoxic effects of the nanoparticles for the A549 (lung adenocarcinoma) and MRC-5 (normal) cell lines was investigated by MTT assay. Furthermore, the effects of Fe3O4@Glucose-Gingerol nanoparticles on the expression of the CASP8, BAX, and BCL2 genes and the activity of Caspase 3 were characterized. The flow cytometry assay (annexin V/PI) was employed to find out the percentage of apoptotic cells. The Fe3O4@Glu-Gingerol NPs were spherical (42-67 nm), without elemental impurity, and with surface charge, DLS size, and magnetic saturation of -47.7 mV, 154 nm, and 35 emu/g, respectively. Fe3O4@Glu-Gingerol NPs showed a remarkable greater toxicity in the A549 cells than normal cell line with the 50 % inhibition concentration (IC50) of 190 and 554 μg/mL, respectively. Treatment of lung adenocarcinoma cells with the Fe3O4@Glu-Gingerol NPs led to an increase in cell apoptosis from 4.6 to 39.48 %. Also, the CASP8 and BAX genes were upregulated by 2.49 and 2.8 folds, respectively, while a downregulation by 0.75 folds was noticed for the BCL2. Moreover, apoptotic features were observed in Fe3O4@Glu-Gingerol NPs treated cells by Hoechst staining, and activation of Caspase 3 by 2.8 folds. This study revealed that the Fe3O4@Glu-Gingerol NPs have antiproliferative effects on the lung adenocarcinoma cell line by activation of intrinsic and extrinsic apoptosis that is a promising feature in cancer treatment.

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