Molecular Docking of Phytochemicals Involved in Apoptotic Pathway and Their Interactions with CASP3, CASP9, and BAX in HepG2 Cell Line

As liver cancer is a leading cause of death all over the world, there is a need to explore new therapeutic strategies. This study presents an in silico analysis of the genes Caspase3 (CASP3), Caspase9 (CASP9), and BCL-2-associated X protein (BAX) in liver cancer cells to evaluate the apoptosis profile following exposure to green-synthesized plant extract. We assessed the modulatory effects of phytochemicals on the apoptotic pathway by means of bioinformatics tools and a publicly available gene expression dataset. Our findings revealed the possible mechanistic basis of the pro-apoptotic activity observed in vitro, utilizing a structure-based molecular docking method. The biologically synthesized AgNPs at a concentration of 50 µg/mL induced an approximately 4-fold increase in the mRNA expression levels of CASP3, CASP9, and BAX compared with chemically synthesized AgNPs, as determined by qPCR. Rutin was the compound with the highest binding affinities toward all three proteins, with ΔG values of −9.3 kcal/mol (Caspase3), −9.1 kcal/mol (Caspase9), and −9.0 kcal/mol (BAX). These findings offer new insights about the molecular mechanisms that support the cytotoxicity of phytochemicals, and simultaneously highlight the potential of green nanotechnology for the development of therapeutic strategies for liver cancer.