Integrative Network Pharmacology and Molecular Docking Analysis of Uncaria gambir Roxb. Against MCF-7 Human Breast Cancer Cells
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Abstract
Breast cancer (BC) remains a leading cause of cancer-related mortality among women, particularly those with estrogen receptor-positive (ER+) disease. The Michigan Cancer Foundation-7 (MCF-7) subtype presents notable therapeutic challenges due to its prevalence and limited response to standard treatments. This study used network pharmacology and molecular docking to assess Uncaria gambir Roxb. (UGR)'s anticancer potential against MCF-7 cells. Active compounds from the ethanol UGR extract were obtained from the literature and screened based on pharmacokinetic and toxicological parameters, including oral bioavailability, drug-likeness, intestinal absorption, LD₅₀, and inactive cytotoxicity. The target genes of compounds and diseases were retrieved from GeneCards. STRING was used to build protein–protein interaction networks, and Cytoscape was employed to visualize them. ShinyGO was utilized to analyze Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Molecular docking was conducted with AutoDock Vina via PyRx 0.98. Four compounds; catechin, epicatechin, hirsutin, and quercetin, met the ADMET selection criteria. A total of 604 overlapping target genes were identified, with TP53, CTNNB1, SRC, and ESR1 serving as major network hubs. Gene Ontology and KEGG analyses confirmed the involvement of these targets in key cancer-related pathways. Catechin and quercetin acted as central modulators. The docking results showed strong affinities to the targets: catechin–TP53 (-7.2 kcal/mol), quercetin–SRC (-8.9 kcal/mol), ESR1 (-8.5 kcal/mol), and epicatechin–ESR1 (-8.8 kcal/mol). The potential of UGR as a source of multi-target natural compounds for BC therapy was demonstrated by these findings, which were on par with or better than reference medications.
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