Molecular Docking, Molecular Dynamics Simulation, and Antiproliferative Study of Ampelocissus thyrsiflora Compounds Targeting PARP in MCF-7 Cells

Abstract

Breast cancer remains the most frequently diagnosed cancer worldwide, and the severe adverse effects associated with conventional chemotherapy underscore the urgent need to discover safer, natural anticancer agents with fewer side effects. This study aimed to investigate the anticancer potential of Ampelocissus thyrsiflora (Blume) Planch, a North Sumatran medicinal plant rich in flavonoids. Initially, in silico analyses were conducted to identify potential bioactive compounds and their molecular targets. The ethanol extract was found to contain seven distinct flavonoid compounds, identified by LC-HRMS. Network pharmacology analysis identified 259 proteins associated with breast cancer. Among these, one compound showed a high interaction score (0.742) with poly (ADP-ribose) polymerase (PARP), a protein that plays a critical role in DNA repair and is highly relevant in breast cancer, highlighting it as a key therapeutic target. Molecular docking revealed strong binding affinities of the compounds to PARP, involving key amino acid residues TYR907, GLY863, SER904, TYR889, ALA898, and LYS903. Molecular dynamics simulations further confirmed stable ligand–protein interactions over a 100-ns trajectory. Subsequently, in vitro validation was performed to confirm the computational findings. The MCF-7 breast cancer cell line was selected for its well-established expression of hormone-responsive pathways and its relevance to studying PARP-associated DNA repair mechanisms in breast cancer. Treatment with the extract resulted in a dose- and time-dependent decrease in cell proliferation. These findings highlight the potential of A. thyrsiflora flavonoids as promising natural candidates for targeted breast cancer therapy.