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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1496664
Mechanism of Apigenin against Breast Cancer Stem Cells: Network Pharmacology and Experimental Validation
Provisionally accepted
Mengdie Ou
1,2
Zhicheng Deng
3
Yonghui Shi
2
Jianxiong He
2
Zicong Ye
2
Ming Guo
2
Guohua Cheng
1*
Junyan Wu
2*
Li Lv
2*- 1 School of Pharmacy, Jinan University, Guangzhou, China
- 2 Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- 3 Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, China
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, down-regulated 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.
Keywords: Apigenin, Breast cancer stem cells, MCF-7 Cells, PI3K/AKT, p53, Network Pharmacology, molecular docking
Received: 15 Sep 2024; Accepted: 31 Oct 2024.
Copyright: © 2024 Ou, Deng, Shi, He, Ye, Guo, Cheng, Wu and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guohua Cheng, School of Pharmacy, Jinan University, Guangzhou, China
Junyan Wu, Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Li Lv, Department of Pharmacy, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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