Ellagic Acid-Conjugated Iron Oxide Nanoparticles Inhibit the Cell Cycle in the G0/G1 Phase and Induce Extrinsic...

Mortalities due to gastric cancer have raised serious health concerns. It is thought that drug delivery using magnetic nanoparticles can be a new solution in cancer treatment. 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, X-ray diffraction, energy-dispersive X-ray spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, dynamic light scattering, and zeta potential analyses were used for physical and chemical characterizations. The percentage of cell viability was determined by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) 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 a real-time polymerase chain reaction. The results showed that the IC₅₀ of Fe₃O₄@Glu-EA nanoparticles for the human gastric adenocarcinoma cell line and human dermal fibroblasts cell line 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 gene in these cells was elevated by 4.91 folds. This study showed that Fe₃O₄@Glu-EA nanoparticles have considerable toxicity for gastric cancer cells and as an efficient platform for delivery of EA to gastric cancer cells, can provide promising outcomes in chemotherapy of gastric cancer.