Ziziphus mauritiana in Triple-Negative Breast Cancer: Integrating Network Pharmacology and In Vitro Evaluation
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Abstract
New metabolites isolated from botanical sources are renowned for having traditional and therapeutic significance. According to ethnopharmacological studies, Ziziphus mauritiana (ZM) is a medicine effective against various diseases, including cancer. However, the underlying mechanism of ZM effectiveness remains unclear. Therefore, this study aimed to determine how ZM affects the treatment of Triple-Negative Breast Cancer (TNBC) using network pharmacology and in vitro validation. A protein interaction network was then constructed to screen hub genes for ZM and TNBC, using STRING database and Cytoscape software. Subsequently, protein module cluster analysis was performed using Cytoscape MCODE plugin. DAVID database was also carried out to assess gene ontology, Kyoto Encyclopedia enrichment, as well as gene and genome pathway analysis for targets common to both ZM and TNBC. CCK-8 assay was used to assess the cytotoxicity of ZM on MDA MB-231 cells. The results showed that there were 5 hub genes for ZM, along with 6 possible active compounds, 93 possible therapeutic targets, and 5 genes affecting TNBC cell death, growth, metastasis, angiogenesis, invasiveness, and chemical resistance. ZM was found to significantly reduce cell viability (p < 0.001). It produced a cytotoxic effect against MDA MB 231 cells and influenced AKT1, MYC, STAT3, as well as TP53, the primary targets in TNBC therapy. These targets and pathways provided a theoretical basis for the development of new drugs that impact drug resistance in TNBC.
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