The apoptosis inducement of green-synthesis silver nanoparticles in medullary thyroid carcinoma cells

Abstract Silver nanoparticles (AgNPs) produced biogenically have emerged as prospective nanotherapeutic agents due to their significant anticancer effectiveness, improved biocompatibility, restricted systemic toxicity, and efficient apoptosis induction. In this study, AgNPs were synthesized utilizing Crocus sativus extract and comprehensively characterised through UV–vis, FT-IR, XRD, FE-SEM, TEM, and DLS analyses. The cytotoxic potential was evaluated using the MTT test on medullary thyroid cancer (TT) cells and normal human liver (WRL-68) cells. The results displayed a dose-dependent decrease in TT cell viability, whereas only a minimal impact was observed on normal cells, even at elevated doses. The determined IC 50 concentrations were 69.58 μg ml −1 against TT cells and 162.7 μg ml −1 for WRL-68 cells, indicating preferential cytotoxicity towards cancer cells. To elucidate the underlying apoptotic mechanisms, caspase-8 and caspase-9 activities were assessed. The findings revealed minimal activation of the extrinsic route, while significant activation of the intrinsic mitochondrial pathway was evident, highlighting the ability of C. sativus -mediated AgNPs to induce apoptosis predominantly. Complementary, cell cycle analysis revealed a redistribution of TT cells following AgNPs exposure, characterized by a reduction in G 0 /G 1 to around 60%, S phase to around 13%, and a marked accumulation in the G 2 /M phase to about 27%. This pattern indicates G 2 /M phase arrest, suggesting that AgNPs treatment interferes with normal DNA replication and mitotic entry. Overall, the present study highlights the promise of green-synthesized AgNPs as a novel nanotherapeutic platform for targeting MTC through coordinated disruption of cell cycle progression and activation of mitochondrial-mediated apoptosis.