Ag nanoparticles green-mediated by Scrophularia striata aqueous extract induce apoptosis via P53 and signal transducer and activator of transcription 3 signaling pathways in gastric cancer cells

Abstract

In the present study, we tried to prepare and formulate an anticancer drug (Silver nanoparticles in aqueous medium using Scrophularia striata leaf extract) for the treatment of gastric cancer. The chemical characterization tests including UV–Visible Spectroscopy (UV-Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), and Field Emission Scanning Electron Microscopy (FE‐SEM) were used for the characterization of silver nanoparticles. In the FE-SEM images, the silver nanoparticles were in an average size of 36.19 nm with the spherical shape. For investigating the antioxidant properties of AgNO3, S. striata aqueous extract, and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene (BHT) as the positive control. IC50 of silver nanoparticles was 97 µg/mL against the DPPH molecules. To survey the cytotoxicity and anticancer effects of AgNO3, S. striata aqueous extract, and AgNPs, MTT assay was used on the gastric cancer cell lines. Silver nanoparticles removed GC1415, NCI-N87 and MKN45 cancer cell lines at the low concentrations. Nanoparticles induced cell apoptosis, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, AgNPs inhibited colony formation compared to their matched control. More significantly, the molecular pathway analysis of AgNPs-treated cells revealed that nanoparticles enhance p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the nanoparticles in human cancer cells. As mentioned, AgNPs had significant anticancer properties against the above cell lines.