Synthesis, characterization, antioxidant and anticancer potential of Kalanchoe pinnata green synthesized silver nanoparticles targeting p53/MDM2 nexus in hepatic cancer: integrated in vitro and in silico study

Globally, hepatocellular carcinoma (HCC) is among the most commonly diagnosed cancers presenting complex treatment modalities. However, the side effects associated with conventional HCC therapeutics are quite detrimental, emphasizing the need to explore alternative therapeutics for the disease. The present report focuses on synthesis, characterization and investigation of the multifunctional biopotential of silver nanoparticles (AgNPs), biosynthesized using Kalanchoe pinnata ethanolic leaf extract (Kp-EtOH). The synthesized nanoparticles (Kp-AgNPs) were characterized by dynamic light scattering (DLS), TEM and FTIR. Results showed that Kp-AgNPs had an average hydrodynamic radius of 4.74 ± 1.41 nm, and a zeta potential of 23.91 ± 0.75 mV, indicative of good stabiliy. TEM images revealed the overall morphology of Kp-AgNPs as being spherical, and the FT-IR analysis showed widening of the peak at ∼3200 cm-1 indicating the reduction of Ag + ions by Kp-EtOH. The GC-MS analysis revealed the presence of 33 bioactive compounds, including β-amyrin with various pharmacological attributes. The antioxidant potential of Kp- AgNPs was evaluated via DPPH and ABTS assays, while their anti-cancer activity against human hepatocellular carcinoma (HepG2) cells was determined through MTT assay, morphological assessment, DAPI staining, ROS and apoptosis assays. The findings also revealed a reduction in viability of the HepG2 cells associated with elevated ROS levels (p < 0.01), leading to substantial morphological abruptions and apoptotic cell death. Molecular docking studies further established the role of β-amyrin in modulating the p53/MDM2 regulatory axis. Collectively, these findings support the development of K. pinnata-based AgNPs as herbal therapeutics against HCC, and various other oxidative disorders, thus confirming their role as novel therapeutic agents.