• Apigenin Impact on Breast Cancer: A Mechanistic Study Based on Network Pharmacology
  • Ali Jabbarzadeh,1 Eisa Kaveh Vernousfaderani,2 Helya Bahavar,3 Kiana Farhadi Nejad,4 Golrokh Farnam,5 Farshad H Shirazi,6,*
    1. IPharmS, Student research committee, Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.
    2. IPharmS, Student research committee, Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.
    3. IPharmS, Student research committee, Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.
    4. IPharmS, Student research committee, Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.
    5. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.
    6. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, I.R.Iran.


  • Introduction: Based on the WHO report, breast cancer (BC) was the most commonly diagnosed cancer among women in 2020, which counted for 1 in every six deaths caused by cancer in women. Humanity has a long history of using plant-derived compounds as medicine, especially for cancer treatment. Flavonoids are among the most important natural compounds with various pharmacological properties, including their significant anti-cancer activities. Apigenin, also known as 4′,5,7-trihydroxyflavone, is a member of the Flavonoids family commonly found in various food plants and herbs such as parsley, onions, oranges, chamomile, and oregano.
  • Methods: In this study, we used Pubchem, Binding DB, SwissTargetPrediction, Similarity Ensemble Approach (SEA), TargetNet, GeneCards, Way2Drug, DAVID, and DisGeNET databases to identify the BC-related Apigenin targets. Furthermore, we used the STRING database to explore the protein-protein interactions of BC-related proteins when exposed to Apigenin and the gene ontology of these proteins. Cytoscape 3.9.1 illustrate the data network. Autodock Vina 4.2 and Discovery Studio 4.5 conducted molecular docking.
  • Results: The gene ontology data revealed that enzyme binding, macromolecular complex, and positive regulation of transcription from RNA polymerase II promoter are the most probable processes under the influence of Apigenin. Based on the network pharmacology, AKT1 and EGFR (Epidermal Growth Factor Receptor) are the most influential targets in relation to BC. The affinity of Apigenin towards AKT1 and SHBG was identical, with releasing the energy of -7.6 Kcal/mol for both. In addition, estimations demonstrate that AKT1 and SHBG are more effective against the MCF7 cell line. Several studies have shown that Apigenin exhibits potent anti-BC activities through the induction of apoptosis and cell proliferation arrest. One study revealed that the inhibition of Akt by Apigenin causes the downregulation of MMP-9, a key promoter for metastasis in cancer cells. EGFR plays an essential role in regulating and maintaining BC cell characteristics such as metastasis, proliferation, and invasion. Apigenin has been proven to decrease the expression of EGFR. These studies validate our finding on Apigenin’s activities against BC.
  • Conclusion: In conclusion, based on the results of recent studies and ours, Apigenin shows great potential as an active agent against several breast cancer cell lines with multiple pathways causing apoptosis and cell cycle arrest.
  • Keywords: Apigenin, Breast Cancer, Network Pharmacology, Molecular Docking