Solanum trilobatum leaf extract-derived silver nanoparticles downregulate the PI3K/AKT/mTOR signaling pathway and attenuate oral squamous cell carcinoma cell proliferation

Abstract

Introduction: Oral cancer’s aggressive nature poses a significant health risk, demanding timely diagnosis and effective treatment. Despite progress in conventional therapies like chemotherapy and surgery, their limitations drive the exploration of alternative strategies. This study assessed Solanum trilobatum-derived silver nanoparticles (AgNPs) in impacting cancer cell cycles, inducing apoptosis, and modulating key pathways, including the phosphoinositide 3-kinase (PI3K)/Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, leveraging phytotherapy and nanotechnology—a promising frontier in cancer treatment. Methods: AgNPs were synthesized through the reduction of ions and stabilized using aqueous leaf extracts of S. trilobatum. After the characterization of AgNPs, the mRNA Gene Expression and mitochondrial membrane potentials (MMPs) were assessed. DNA fragmentation was done and DNA pattern by gel documentation system was observed. The study also assessed the modulation of the PI3K/Akt/mTOR cascade, impacting tumor growth and proliferation. Results: Biosynthesized AgNPs were characterized using UV-visible spectrophotometry (UVvis), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy. DNA fragmentation exhibited a typical ladder pattern. Dose-dependent changes in MMP were observed in the treated oral cancer cells. The effect of S. trilobatum-derived AgNPs in targeting the cell signaling pathway correlated significantly with their anticancer potency (P<0.001). Conclusion: This study reveals S. trilobatum leaf extract-based AgNPs as a natural cytostatic agent against oral squamous carcinoma. Utilizing nature’s resources and nanoscale science, they hold promise for enhancing oral cancer treatment outcomes and survival rates.