Biochemical and cellular effects of propolis and silver nanoparticle combination: apoptotic signaling and antibiofilm activity.

BACKGROUND: Cancer and antimicrobial resistance represent two of the most critical challenges to global health. The limitations of conventional therapies, including severe side effects, drug resistance, and high failure rates, necessitate the exploration of novel and synergistic treatment strategies. Natural products like propolis and nanotechnology-based agents such as silver nanoparticles (AgNPs) have emerged as promising candidates due to their multifaceted biological activities. This study investigated the synergistic anticancer and antibacterial effects of Turkish propolis and AgNPs. METHODS: The selective cytotoxicity of propolis and AgNPs was evaluated on human breast adenocarcinoma (MCF-7) and non-tumorigenic mammary epithelial (MCF-10 A) cell lines using MTT assays. Apoptosis was assessed by Annexin V/PI staining and cell cycle distribution by flow cytometry. Mitochondrial membrane potential was analyzed using JC-1 staining, and the expression of apoptosis-related proteins (Bcl-2, p38 MAPK) was examined by Western blot. Antibacterial and antibiofilm efficacy against carbapenem-resistant Acinetobacter baumannii and Escherichia coli were determined by broth microdilution, checkerboard, and biofilm inhibition assays. RESULTS: Propolis and AgNPs exhibited selective, dose-dependent cytotoxicity against MCF-7 cancer cells (IC50: 0.233 mg/mL and IC25: 3.12 µg/mL, respectively) while sparing MCF-10 A cells. Their combination synergistically enhanced apoptosis (47.42% vs. 9.89% and 14.74% for single agents), induced G1 cell cycle arrest, and promoted mitochondrial depolarization. Western blot analysis confirmed the synergistic downregulation of the anti-apoptotic protein Bcl-2. In antibacterial assays, the propolis-AgNP combination demonstrated synergistic effects (FICi: 0.375 for A. baumannii; 0.5 for E. coli) and significantly reduced preformed biofilms by up to 81.3% and 76.4%, respectively, outperforming propolis alone. CONCLUSION: Turkish propolis and AgNPs synergistically enhance anticancer and antibacterial effects by selectively inducing apoptosis in breast cancer cells and suppressing carbapenem-resistant pathogens and their biofilms. This dual-action approach highlights the potential of combining natural products with nanomaterials as innovative strategies against cancer and multidrug-resistant infections.