Ag-doped ZnO nanoparticles synthesized through green method using Artemisia turcomanica extract induce cytotoxicity and apoptotic activities against AGS cancer cells: an in vitro study

Artemisia turcomanica extract was utilized to green synthesize Ag, ZnO, and Ag-doped ZnO nanoparticles (NPs). The aim of this research was to assess the anticancer activity of these NPs against AGS gastric cancer cells. Ag-doped ZnO, undoped ZnO, and Ag NPs were synthesized and characterized by X-ray powder diffraction, UV-visible spectroscopy, Field Emission Scanning Electron Microscope, Fourier Transform Infrared Spectrometer, Transmission Electron Microscopy, and zeta potential. The anti-proliferative activity of the biogenic synthesized NPs was evaluated against AGS cancer cells. Apoptosis induction and cell cycle arrest were determined using flow cytometry. The expression levels of Caspase 3 (CASP3), Caspase 9 (CASP9), BCL2-associated X (BAX), and BCL2 apoptosis regulator (BCL2) genes were measured by qRT-PCR. The size of the ZnO, Ag, and Ag-doped ZnO NPs is estimated between 24 and 45, 17 and 31, and 11 and 49 nm, respectively. The zeta potential values of Ag, ZnO, and Ag-doped ZnO NPs were measured - 17.05 +/- 0.36, - 17.60 +/- 0.42, and - 16.20 +/- 0.56 mV, respectively, which indicates the proper stability of NPs. The spherical synthesized NPs and plant extract showed a cytotoxic effect on AGS cancer cells. Inhibitory concentration (IC50) values of the extract, Ag, ZnO, and Ag-doped ZnO NPs were 234.65, 18.32, 9.15, and 5.31 mu g/mL, respectively, which indicated great anticancer activity of Ag-doped ZnO NPs. Early apoptosis induced by treatment using extract, Ag, ZnO, and Ag-doped ZnO NPs were 3.26, 5.86, 15.40, and 11.3%, and 7.05, 15.5, 11.10, and 23.55% of the cells were engaged in late apoptosis, respectively. This indicated the ideal apoptotic effects of Ag-doped-ZnO NPs. The biosynthesized Ag-doped-ZnO NPs also could arrest the AGS cells in the sub-G1 phase of the cell cycle. The Ag-doped-ZnO NPs could significantly up-regulate the expression of pro-apoptotic (CASP3, CASP9, BAX) and down-regulate the expression of BCL2 genes compared to other treated groups (P < 0.001). These findings confirmed that the synthesized biogenic NPs are good candidates for cancer therapy in the biomedical field as an anticancer agent. Graphical abstract The biogenic synthesis of Ag-doped ZnO nanoparticles was performed using Artemisia turcomanica extract. For the synthesis of Ag-doped ZnO NPs, Zinc acetate was mixed with AgNO3. Then, A. turcomanica extract was added. The color change of the solution indicated the synthesis of Ag-doped ZnO NPs. After cellular uptake of Ag-doped ZnO nanoparticles into the cancer cells, ROS generation, mitochondrial damage, apoptosis induction, and cell cycle arrest in sub-G1 occurred. [GRAPHICS] .

Automated summary

Artemisia turcomanica extract was used to synthesize Ag, ZnO, and Ag-doped ZnO nanoparticles. The anticancer activity of these nanoparticles against AGS gastric cancer cells was evaluated. The Ag-doped ZnO nanoparticles showed significant anticancer activity and induced apoptosis and cell cycle arrest. Rating: 8 out of 10.