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2000
Volume 25, Issue 8
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored.

Objective

In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and experiments.

Methods

The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) analysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, experiments were performed to assess the accuracy of predicted target genes.

Results

The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrichment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signaling. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispolon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC.

Conclusion

In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and experiments, providing a new insight into the mechanism of TCM monomer against TNBC.

© 2025 Bentham Science Publishers
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2025-10-23

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Bioinformatics Strategy for Investigating the Mechanism of Hispolon in the Treatment of Triple-Negative Breast Cancer s with In vitro Experiments
Curr. Cancer Drug Targets< 25, 984 (2025); https://doi.org/10.2174/0115680096313623240801070716
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  • Article Type:     Research Article
Keyword(s): anti-canccer activity; Hispolon; in vitro experiments; network pharmacology; target protein; triple-negative breast cancer

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