Trevesia palmata-derived terpenoid-rich silver nanoparticles induce apoptosis and upregulate p21/CAV1 proteins in gastric cancer cells

Abstract

Cancer remains one of the most prevalent and deadly diseases, ranking among leading global causes of morbidity and mortality. This study presents the green synthesis of silver nanoparticles using Trevesia palmata leaf extract (Trp-AgNPs) and evaluates their anticancer efficacy. Trp-AgNPs formation was confirmed by the color transition of the solution from transparent to brown, along with a prominent UV-Vis absorption peak at 436 nm. X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) confirmed the crystalline structure of the Trp-AgNPs and the presence of biomolecules contributing to reduction and stabilization. Transmission electron microscopy (TEM) analysis identified spherical nanoparticles with an average diameter of 17.84 ± 8.28 nm. QToF-MS analysis indicated that 26 different compounds, including 14 bioactive terpenoids, were bound to the surface of the silver nanoparticles. The anticancer properties of Terpenoid-rich Trp-AgNPs were evaluated across four cancer cell lines (MKN45, HepG2, MCF7, and A549), with MKN45 demonstrating the highest sensitivity (IC₅₀ = 0.5 μg mL⁻¹). Flow cytometry revealed dose-dependent apoptosis in MKN45 cells induced by Trp-AgNPs. Trp-AgNPs upregulated the transcription of Caspase 8, Caspase 3, P21, and Caveolin-1 (CAV1) genes. Significantly, the mRNA expression of P21 increased by more than five-fold, while CAV1 demonstrated an approximately eleven-fold increase, indicating their potential role in cytotoxicity. Additionally, strong binding of nanoparticle surface compounds to anti-apoptotic proteins, as shown by molecular docking, reveals how Trp-AgNPs induce apoptosis signaling in gastric cancer cells. These findings highlight the potential of Trp-AgNPs as a targeted, eco-friendly therapeutic strategy for gastric cancer.