Affiliation:
1. Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran
2. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
3. Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Abstract
Abstract
Background:
Gastric carcinoma is the fourth most common malignancy worldwide. Conjugation of metal nanoparticles with thiosemicarbazones has shown considerable anti-cancer potential.
Materials and Methods:
Zinc oxide nanoparticles (ZnO NPs) were synthesized, functionalized by glutamine, and conjugated with thiosemicarbazide (ZnO@Gln-TSC). Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy imaging, energy-dispersive X-ray, DLS, and zeta potential were used to characterize the NPs. The toxicity of ZnO NPs, TSC, ZnO@Gln-TSC NPs, and oxaliplatin in AGS cells and ZnO NPs and ZnO@Gln-TSC NPs in HEK293 cells was investigated by MTT assay. Cell apoptosis was evaluated by flow cytometry, caspase-3 activity, and Hoechst staining assays. The intra-cellular reactive oxygen species level and expression level of the CASP3 gene in AGS cells treated with ZnO@Gln-TSC NPs were evaluated.
Results:
The NPs were in the size range of 20 to 70 nm. The DLS and zeta potential were 374 nm and -31.7 mV, respectively. In MTT, the IC50 of ZnO, TSC, oxaliplatin, and ZnO@Gln-TSC NPs for AGS cells were 130, 80.5, 67.7, and 9.8 μg/mL, respectively, and the IC50 of ZnO and ZnO@Gln-TSC NPs for HEK293 cells were 215 and 150.5 μg/mL, respectively. Flow cytometry showed higher apoptosis in the cell treated with the NPs and TSC. Apoptotic features, including cell shrinkage, were recognized. A significant increase of 5.9 folds in the level of ROS was noticed. The activity of caspase-3 and the expression level of the CASP3 gene were increased by1.83 and 1.6 folds after exposure to ZnO@Gln-TSC NPs, respectively.
Conclusion:
This study revealed the anti-cancer potential of ZnO@Gln-TSC NPs to be used for gastric cancer treatment after further in vitro and in vivo assays.