Ampelopsin Inhibits Breast Cancer Glucose Metabolism Reprogramming Based on Network Pharmacology and Molecular Docking

Abstract

Background: Breast cancer (BC) is the most frequent type of gynecology tumors with high morbidity and mortality. Ampelopsin, the main active compound of Ampelopsis grossedentata, exerts an anti-tumor effect on a variety of cancers. However, the anti-cancer role of ampelopsin in BC remains unclear. The aim of this study is to explore the mechanism of ampelopsin against breast cancer. Materials and Methods: The target genes of ampelopsin in the treatment of breast cancer were determined and analyzed by network pharmacology and molecular docking. Cytoscape software was used to identify the core target genes and construct a protein–protein interaction (PPI) network. Discovery Studio software was used to perform the molecular docking of ampelopsin and core genes and glycolytic metabolic enzymes. Results: In total, 25 potential target genes of ampelopsin were screened out. The core target genes of ampelopsin against breast cancer were AKT1, ESR1, ESR2, NCOA1, HSP90AA1, NCOA2, BECN1, COMT, HMOX1, and CDK6, with AKT1, ESR1 and ESR2 considered as the key target proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ampelopsin inhibited breast cancer via modulating the estrogen signaling pathway, apoptosis regulation, carbohydrate metabolism, and inflammation. Molecular docking analysis showed that ampelopsin possessed a stable binding ability to regulate the three target proteins and glycolytic metabolic enzymes such as ALDOA and LDHA. Conclusions: Ampelopsin may inhibit the proliferation of breast cancer cells by acting on AKT and estrogen-related glucose metabolic pathways and inhibiting the enzymes involved in glycolysis and oxidative phosphorylation.