Mechanism of Apigenin against breast cancer stem cells: network pharmacology and experimental validation
Mengdie Ou1,2, Zhicheng Deng3, Yonghui Shi2
1School of Pharmacy, Jinan University, Guangzhou, China.
Abstract:
Apigenin (API), a traditionally sourced flavonoid, is recognized for its anti-neoplastic properties. Despite well-documented effects on tumorigenesis, the detailed therapeutic impact on breast cancer stem cells (BCSCs) and the associated molecular mechanisms are yet to be clarified. The objective of this study is to elucidate the therapeutic effects of API on BCSCs and to uncover its molecular mechanisms through network pharmacology and experimental validation. Interactions of API with candidate targets were examined through target screening, enrichment analysis, construction of protein-protein interaction networks, and molecular docking. MCF-7-derived BCSCs were utilized as a model system to investigate and substantiate the anti-BCSC effects of API and the underlying mechanism. Molecular docking studies have shown that API and TP53 exhibit favorable binding affinity. Compared with the negative control group, API effectively suppressed the expression of BCSC-related proteins such as ALDH1A1, NANOG, EpCAM, and MYC, downregulated p-PI3K and p-AKT, and upregulated p53. This study demonstrates that API can play an anti-BCSC role by regulating the PI3K/AKT/p53 pathway in BCSCs of MCF-7 cells, highlighting its potential as a therapeutic agent for targeting BCSCs.
Insights
Apigenin (API) effectively targets breast cancer stem cells (BCSCs) by regulating the PI3K/AKT/p53 pathway. This flavonoid demonstrates potential as a therapeutic agent against BCSCs in MCF-7 cells.
Area of Science:
- * Biochemistry and Molecular Biology
- * Cancer Research
- * Pharmacology
Background:
- * Apigenin (API), a flavonoid, exhibits anti-neoplastic properties, but its specific effects on breast cancer stem cells (BCSCs) and underlying mechanisms remain unclear.
- * BCSCs are crucial for tumor initiation, progression, and therapeutic resistance, making them a key target for cancer therapy.
Purpose of the Study:
- * To investigate the therapeutic effects of Apigenin (API) on breast cancer stem cells (BCSCs).
- * To elucidate the molecular mechanisms by which API exerts its anti-BCSC effects using network pharmacology and experimental validation.
Main Methods:
- * Network pharmacology approach including target screening, enrichment analysis, and protein-protein interaction network construction.
- * Molecular docking to assess API's binding affinity with candidate targets, particularly TP53.
- * Experimental validation using MCF-7-derived BCSCs to evaluate API's impact on key protein expression and signaling pathways.
Main Results:
- * Molecular docking indicated favorable binding between API and TP53.
- * API treatment significantly suppressed BCSCs by downregulating proteins such as ALDH1A1, NANOG, EpCAM, and MYC.
- * API modulated the PI3K/AKT/p53 pathway, downregulating p-PI3K and p-AKT while upregulating p53 expression.
Conclusions:
- * Apigenin (API) demonstrates significant anti-BCSC activity in MCF-7 cells.
- * The therapeutic effect of API on BCSCs is mediated through the regulation of the PI3K/AKT/p53 signaling pathway.
- * API holds promise as a potential therapeutic agent for targeting breast cancer stem cells.
