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

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 (Ag2S NPs) synthesized with sweet cherry (Prunus avium L.), gemcitabine (GEM), a chemotherapy drug, and their combination (Ag2S NPs—GEM) on PANC-1 cancer cell lines was evaluated by MTT method. Additionally, the interaction of Ag2S NPs, GEM, and their combination with DNA was examined by conducting agarose gel electrophoresis. Also, interactions of Ag2S NPs, GEM, and their combination (Ag2S 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 Ag2S NPs was 24 hours (IC50: 75.77 µg/mL), while the most effective results for gemcitabine were obtained at 72 hours (IC50: 32.77 µg/mL). The combined application of Ag2S NPs and GEM produced significantly more effective results compared to monotherapy (IC50: 18.97 µg/mL in 72 h). DNA cleavage study showed that both Ag2S NPs and GEM bind to DNA, especially Ag2S NPs has affinity for G-G bases. The Ag2S NPs—GEM combination showed highly favorable binding affinities compared to Ag2S and metabolites of GEM, particularly against thymidylate synthase (ΔG = −6.52 kcal/mol) and DNA polymerase alpha catalytic core (ΔG = −6.65 kcal/mol), correlating with its potent cytotoxicity in PANC-1 cells. Additionally, docking simulations with B-DNA revealed that Ag2S NPs—GEM exhibits the strongest DNA-binding affinity (ΔG = −7.93 kcal/mol), acting as an effective DNA binder that may enhance cytotoxicity in PANC-1 cells.