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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 Mengdie Ou 1,2Zhicheng Deng Zhicheng Deng 3Yonghui Shi Yonghui Shi 2Jianxiong He Jianxiong He 2Zicong Ye Zicong Ye 2Ming Guo Ming Guo 2Guohua Cheng Guohua Cheng 1*Junyan Wu Junyan Wu 2*Li Lv 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.