Identifying the anti-metastasis effect of Anhydroicaritin on breast cancer: Coupling network pharmacology with experimental validation

Epimedium brevicornu Maxim. and Cullen corylifolium (L.) Medik. are part of a traditional Chinese medicine (TCM) drug pair (ECDP) widely used in the clinical treatment of breast cancer (BC). Both drugs have been proven to have anti-tumor effect. However, the active ingredients and molecular mechanis...

Full description

Saved in:
Bibliographic Details
Published in:Journal of ethnopharmacology 2022-07, Vol.293, p.115326-115326, Article 115326
Main Authors: Shi, Youyang, Wu, Yuanyuan, Li, Feifei, Zhang, Yang, Hua, Ciyi, Yang, Jianfeng, Zheng, Jinzhou, Chen, Lili, Wei, Zheng, Yue, Haiyan, Sun, Chenping, Zhou, Xiqiu, Liu, Sheng
Format: Article
Language:English
Subjects:
Anhydroicaritin
Breast cancer
Experimental validation
Molecular docking
Network pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Epimedium brevicornu Maxim. and Cullen corylifolium (L.) Medik. are part of a traditional Chinese medicine (TCM) drug pair (ECDP) widely used in the clinical treatment of breast cancer (BC). Both drugs have been proven to have anti-tumor effect. However, the active ingredients and molecular mechanism of ECDP remain to be explored. Aim of the study: To explore the efficacy and potential mechanisms of actions of herb pair through network pharmacology and in vitro and in vivo experiments. The active ingredients of ECDP were identified using high-performance liquid chromatography. The corresponding potential target genes for ECDP components and BC were extracted from established databases, and the protein–protein interaction network of shared genes was constructed using STRING database. The effective ingredients and targets of ECDP for BC were obtained through the TCMSP database and GeneCards database. The potential targets and pathways were selected through the protein interaction network and enrichment analysis. Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of Anhydroicaritin (AHI) on BC. AHI is the potential candidate active ingredient of ECDP through TCMSP. Molecular docking revealed that AHI has excellent binding ability with TP53, VEGFA, MMP2, and Met. In vitro experiment results showed that AHI inhibits the growth of MDA-MB-231, 4T1, MCF-7, and SK-BR-3 BC cells. The inhibitory effect of AHI on triple-negative BC cells is more obvious. With the increase of AHI concentration, the colony-forming, migration, and metastasis abilities of the MDA-MB-231 and 4T1 cells gradually decreases. In addition, Western blot and reverse transcription polymerase chain reaction analyses results indicated that AHI downregulates HIF-1α/VEGFA signaling in triple-negative BC cells. AHI inhibits tumor growth and lung metastasis while downregulating the expression of HIF-1α and VEGFA. AHI may play an anti-BC effect by inhibiting cancer cell proliferation, invasion, and metastasis. The results of this study may provide a theoretical basis for AHI research and the clinical application of ECDP in BC. [Display omitted]
ISSN:0378-8741
1872-7573
DOI:10.1016/j.jep.2022.115326