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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

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Abstract

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 μg/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.

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Acknowledgements

The authors would like to thank the laboratory of Islamic Azad University.

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Authors and Affiliations

  1. Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran

    Fatemeh Mirzaee Rad & Farzaneh Tafvizi

  2. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Noorbazargan

  3. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Alireza Iranbakhsh

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  1. Fatemeh Mirzaee Rad
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  2. Farzaneh Tafvizi
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  3. Hassan Noorbazargan
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  4. Alireza Iranbakhsh
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Contributions

FMR: Data curation, formal analysis, methodology, writing—original draft. FT: Methodology, project administration, data curation, supervision, writing—review & editing. HN: Assisted in performing the cell culture experiments. AI: review & editing of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Farzaneh Tafvizi.

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Mirzaee Rad, F., Tafvizi, F., Noorbazargan, H. et al. 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. J Nanostruct Chem (2023). https://doi.org/10.1007/s40097-023-00528-2

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