Prostate cancer cells often develop mechanisms to evade conventional therapies. Nanomedicine offers the potential for targeted drug delivery, improved tumor accumulation, and reduced systemic toxicity. This study biosynthesizes silver nanoparticles (NPP/AgONPs) functionalized with propolis, evaluates their antibacterial efficacy against uropathogenic strains of Escherichia coli (E. coli), and assesses their cytotoxic effect on cancer cell proliferation using the PC-3, human prostate epithelial cell line.

The synthesized NPP/AgONPs physiochemical parameters were characterized, followed by in vitro assays to evaluate their antibacterial activity against multiple uropathogenic E. coli strains; determining the cytotoxicity against HPrEC and PC-3 cells by measuring cytotoxicity (CC₅₀) and inhibition concentration (IC₅₀), respectively; analyzing cell cycle distribution and apoptosis via flow cytometry; and quantifying the reactive oxygen species (ROS), Caspase 3, and Caspase 8 expression in treated cells to elucidate mechanisms of cell death and growth inhibition.

NPP/AgONPs exhibited an average particle size of 22 nm, with four major X-ray diffraction (XRD) peaks corresponding to Joint Committee on Powder Diffraction Standards (JCPDS) No. 01-1164, confirming their crystallinity. Moreover, the UV–vis absorbance at 390 nm yielded an energy gap of 2.45 eV. Antibacterial testing showed potent activity against the tested E. coli strains. In HPrEC and PC-3 cells, the CC₅₀ was 262.04 µg/mL, while the IC₅₀ was 25.34 μg/mL, respectively. Flow cytometry revealed increased apoptosis in the NPP/AgONPs-treated group across all stages, including early, late, and dead cells, compared with the controls. ROS, Caspase 3, and Caspase 8 levels were inflected in NPP/AgONPs-treated cells, showing apoptotic and growth-inhibitory effects.

The propolis coating improves the nanoparticles’ biocompatibility while enabling potent ROS-mediated apoptosis and cell-cycle disruption in PC-3 cells. These findings support the potential of NPP/AgONPs as a synergistic therapeutic platform, though optimization of dosing, detailed mechanism elucidation, and assessment of long-term safety are warranted.