Anticancer activity of an apigenin-functionalized silica-coated silver oxide nanocomposite against human gastric adenocarcinoma cells (AGS): in vitro and in silico analysis

Silver nanoparticles show promise anticancer agents, yet their clinical translation is hindered by poor bioavailability and nonspecific toxicity. In this study, we developed an apigenin-functionalized silica-coated silver oxide nanocomposite (Ag2O@SP@Apigenin) and evaluated its anticancer activity against AGS human gastric adenocarcinoma cells. Silver nanoparticles were synthesized via chemical reduction, followed by silica-coated using 3-chloropropyltrimethoxysilane, and functionalization with apigenin under alkaline conditions. Successful synthesis and surface modification were confirmed by FTIR, FE-SEM, TEM, TGA, and complementary analyses. The nanocomposite exhibited a spherical morphology with an average size of 99.45 nm. Thermal analysis revealed high stability, with only 2.572% weight loss and structural integrity maintained up to 303 °C. MTT assays demonstrated dose-dependent cytotoxicity of Ag2O@SP@Apigenin against AGS gastric cancer cells, with IC50 values of 41.45 µg/mL and 34.41 µg/mL after 24 and 48 h, respectively. In addition, Ag2O@SP@Apigenin exhibited IC50 values of 51.73 µg/mL and 35.29 µg/mL on HT-20 colorectal cancer cells after 24 and 48 h, respectively. Similarly, the IC50 values were 38.84 µg/mL and 16.733 µg/mL against U87 glioblastoma cancer cell after 24 and 48 h, respectively. In contrast, both apigenin powder and Ag2O@SP nanocomposites reduced cancer cell viability to a significantly greater extent than did the Ag2O@SP@Apigenin composite. Wound-healing assays indicated that Ag2O@SP@Apigenin inhibited AGS cell migration by 42.99%±17.38% after 24 h. Q-RT-PCR analysis revealed downregulation of miR-181a (0.36 ± 0.03 fold), along with upregulation of its potential targets, including the apoptotic genes APAF1 (2.15 ± 0.09 fold), P53 (1.71 ± 0.04 fold), and CASP9 (1.55 ± 0.23 fold), in treated AGS cells. Additionally, downregulation of tumor-suppressive miR-34a was observed, accompanied by downregulation of its target genes involved in cell migration including MMP9 (0.16 ± 0.04 fold), CTNNB1 (0.27 ± 0.08 fold), and EGFR (0.08 ± 0.01 fold) genes was observed in AGS treated cells. Furthermore, in silico molecular docking studies predicted that apigenin effectively interacts with the active sites of key proteins involved in cell proliferation and migration (EGFR, β-catenin, APAF1, MMP2, and MMP9), highlighting the important contribution of apigenin to the anticancer potential of Ag2O@SP@Apigenin. Collectively, these results indicate that apigenin functionalization combined with a protective silica coating yields a silver-based nanocomposite with improved physicochemical stability and multi-target anticancer effects in vitro. The findings are limited to in vitro and computational analyses. This integrated mechanism supports further investigation of the nanocomposite as a potential therapeutic for gastric cancer.