Induction of p53 mediated mitochondrial apoptosis and cell cycle arrest in human breast cancer cells by plant mediated synthesis of silver nanoparticles from Bergenia ligulata (Whole plant)

Abstract

The biological synthesis of nanoparticles is a growing research trend because it has numerous pharmaceutical and biomedical applications. The present study describes the preparation, characterization and anti-cancer evaluation of silver nanoparticles synthesized using an aqueous extract of Bergenia ligulata whole plant as a reducing agent. The physiochemical properties of the Bergenia ligulata silver nanoparticles (BgAgNPs) were measured by ultraviolet–visible spectrophotometry, Fourier transform infrared spectrophotmetry (FTIR), X-ray powder diffraction (XRD) and Scanning electron microscopy (SEM) analysis for identifying functional groups, crystallinity, structural and morphological features, respectively. Further, BgAgNps, along with the Bergenia ligulata aqueous extract (BgAE), were investigated for their effects on cell proliferation and apoptosis through MTT, colony-forming assay, wound-healing assay and flow cytometry-based approaches. The cytotoxic effects were more pronounced in cells treated with BgAgNps in comparison to BgAE. These effects were evidenced by the decreasing cell viability, migration capacity and loss of characteristic morphological features. In addition, BgAgNps unveiled significant induction of apoptosis in human breast cancer (MCF-7) cells, possibly through oxidative stress-mediated reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP). Moreover, molecular mechanism-based studies revealed that BgAgNps robustly augmented p53 levels and pro-apoptotic downstream targets of p53 like Bax and cleaved caspase 3 in MCF-7 cells. Of note, BgAgNps had little or no cytotoxic effect on p53-deficient cancer cells (Mda-mb-231 and SW-620). These findings confirm that the BgAgNPs exhibited superior anti-cancer potential and could be exploited as a promising, cost-effective, and environmentally benign strategy in treating this disease in the future.