Evaluation of the Cytotoxicity and Molecular Docking Properties of the Green Synthesis of Ag2S Nanoparticles

Abstract Pancreatic cancer is a type of cancer that is aggressive and has a high mortality rate with a five-year survival rate. The primary treatment option commonly used today is chemotherapy, which has very severe side effects. Considering all these side effects, the search for a new treatment for pancreatic cancer is extremely important. In this study, the cytotoxicity effect of silver sulfide nanoparticles (Ag 2 S NPs) synthesized with sweet cherry ( Prunus avium L.), gemcitabine (GEM), a chemotherapy drug, and their combination (Ag 2 S NPs—GEM) on PANC-1 cancer cell lines was evaluated by MTT method. Additionally, the interaction of Ag 2 S NPs, GEM, and their combination with DNA was examined by conducting agarose gel electrophoresis. Also, interactions of Ag 2 S NPs, GEM, and their combination (Ag 2 S NPs—GEM) with key enzymes involved in nucleotide synthesis and DNA replication were investigated using molecular docking. The cytotoxicity results in PANC-1 cancer cell lines indicated that the most effective incubation period for Ag 2 S NPs was 24 hours (IC 50 : 75.77 µg/mL), while the most effective results for gemcitabine were obtained at 72 hours (IC 50 : 32.77 µg/mL). The combined application of Ag 2 S NPs and GEM produced significantly more effective results compared to monotherapy (IC 50 : 18.97 µg/mL in 72 h). DNA cleavage study showed that both Ag 2 S NPs and GEM bind to DNA, especially Ag 2 S NPs has affinity for G-G bases. The Ag 2 S NPs—GEM combination showed highly favorable binding affinities compared to Ag 2 S and metabolites of GEM, particularly against thymidylate synthase (Δ G = −6.52 kcal/mol) and DNA polymerase alpha catalytic core (Δ G = −6.65 kcal/mol), correlating with its potent cytotoxicity in PANC-1 cells. Additionally, docking simulations with B-DNA revealed that Ag 2 S NPs—GEM exhibits the strongest DNA-binding affinity (Δ G = −7.93 kcal/mol), acting as an effective DNA binder that may enhance cytotoxicity in PANC-1 cells.