Silver nanoparticles combine with Nigella sativa oil to potentiate apoptosis in cervical cancer

Cervical cancer remains a global health challenge, necessitating innovative therapies that enhance tumor-specific apoptosis while sparing healthy tissues. This study investigates the combined potential of Nigella sativa oil (NS) and silver nanoparticles (AgNPs) in inducing apoptosis in HeLa cervical cancer cells. NS, rich in thymoquinone, modulates apoptotic pathways (Bax/Bcl-2, p53, caspase-9), while AgNPs trigger oxidative stress and genomic instability. We hypothesized that their combination would amplify apoptotic efficacy through complementary mechanisms. HeLa cells were treated with AgNPs (1–10 µg/mL) and with a combination of a selected dose of AgNPs (5 µg/mL) and NS (100–250 µg/mL). Cytotoxicity, apoptosis (as assessed by Annexin V/PI staining and acridine orange/ethidium bromide staining), and gene expression (Quantitative Real-Time Polymerase Chain Reaction, qRT-PCR) were evaluated. Gas Chromatography-Mass Spectrometry (GC-MS) confirmed NS’s bioactive composition, while Scanning Electron Microscopy (SEM)/Fourier Transform Infrared Spectroscopy (FTIR) characterized AgNPs. The results demonstrated dose-dependent apoptosis. The most effective combination was 5 µg/mL AgNPs + 150 µg/mL NS, which induced 29.1% early apoptosis. Pro-apoptotic genes (BAX, BAK, p53, caspase-9) were upregulated (3.2–4.8-fold), while BCL-2 was suppressed (0.28-fold). This study unveils a novel combinatorial strategy leveraging NS’s epigenetic regulation and AgNPs’ cytotoxic effects, suggesting a promising avenue for future research. The findings underscore the potential of plant-nanoparticle synergy in oncology. Future in vivo studies are warranted to validate the clinical applicability.