Ellagic Acid-Conjugated Iron Oxide Nanoparticles Inhibit the Cell Cycle in the G0/G1 Phase and Induces Extrinsic Apoptosis in Gastric Cancer Cell Line.

Abstract

In this study, the effects of iron oxide nanoparticles functionalized with glucose and conjugated with Ellagic acid (EA) on gastric cancer cells were evaluated. (Fourier Transform Infrared Spectroscopy) FT-IR, (X-ray diffraction) XRD, (Energy-dispersive X-ray spectroscopy) EDS, (Field emission scanning electron microscopy) FE-SEM, (Transmission electron microscopy) TEM, (Thermogravimetric analysis) TGA, (Dynamic light scattering) DLS and zeta potential analyses were used for physical and chemical characterizations. The percentage of cell viability was determined by MTT assay, and cell apoptosis level and cell cycle analysis were assayed using flow cytometry. Also, the expression level of the caspase-8 gene was evaluated using real-time PCR. The results showed that the IC50 of Fe3O4@Glu-EA nanoparticles for the human gastric adenocarcinoma cell line (AGS) and human dermal fibroblasts cell line (HDF) was 109 and 211µg/mL. Based on the flow cytometry results, the synthesized nanoparticles increased cell cycle inhibition at the G0/G1 phase and caused a significant increase in early and late apoptosis in cancer cells. Alterations in nuclear morphology such as chromatin condensation and fragmentation in favor of apoptosis were evident in cancer cells treated with the nanoparticles, and the expression of the caspase-8 (CASP8) gene in these cells was elevated by 4.91 folds.