Phytofabricated Silver Nanoparticles From <i>Vaccinium arctostaphylos</i> L.: Anticancer Activity Against Breast Cancer Cells via Apoptosis Induction and Growth Suppression

This study investigates the anticancer efficacy of phytofabricated silver nanoparticles (VACAgNPs) derived from <i>Vaccinium arctostaphylos</i> L. (VAC) against molecularly distinct breast cancer subtypes (MCF-7: hormone-responsive; 4T1/MDA-MB-231: triple-negative). Hydroalcoholic VAC fruit extract, characterized by LC-ESI/MS (71 phenolic compounds, including quercetin-3,7-diglucoside and kaempferol galloylglucoside) and GC-MS (methyl 3,5-bis(ethylamino)benzoate, 26.71%), served as a dual reducing-capping agent for green nanoparticle synthesis. FE-SEM and DLS confirmed spherical VACAgNPs (mean size: 124.67 nm; zeta potential: -6.32 mV) with 66.82 wt% Ag content. In vitro assays revealed dose- and time-dependent cytotoxicity, with 100 μM VACAgNPs reducing viability to 41.0% ± 6.1% (MCF-7), 39.3% ± 6.1% (4T1), and 30.6% ± 5.6% (MDA-MB-231) at 48 h, outperforming cisplatin in caspase-3-deficient MCF-7 cells. Mechanistic studies demonstrated ROS-mediated apoptosis via Bax/Bcl-2 ratio modulation (14.0-fold increase in MDA-MB-231) and Caspase-3 activation (3.91-fold), alongside oxidative stress regulation: FRAP increased to 6.42 ± 0.81 μmol/mL (49.6% above control), while MDA and NO decreased by 59.2% and 31.5%, respectively. The nanoparticles' bioactivity correlated with VAC's antioxidant profile (TPC: 91.06 ± 9.16 mg GAE/g; FRAP: 9520.12 ± 56.46 mmol Fe²⁺/mg), overcoming phytochemical bioavailability limitations through enhanced targeting. These findings establish VACAgNPs as a sustainable therapeutic candidate, offering subtype-agnostic efficacy via dual apoptosis induction and redox modulation, while mitigating chemotherapy-associated toxicity. The study provides critical preclinical evidence for advancing plant-nanoparticle synergism in precision oncology.