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Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action

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Abstract

Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound, its mechanism of action has not been fully elucidated. In this study, we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA on various types of human malignancies including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancers. In this context, after identifying and extracting EA-affected human genes/proteins that have been reported in various references, we built the related gene networks and determined functional hub genes. In addition, docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound. Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers. Moreover, different cellular signaling pathways are affected by this natural compound. Generally, it turned out that EA probably exerts most of its anticancer activities, through induction of apoptosis, as well as P53 and WNT signaling pathways, and also by affecting the expression of several hub genes such as CDKN1A, CDK4, CDK2, CDK6, TP53, JUN, CCNA2, MAPK14, CDK1, and CCNB1 and especially interactions with some related proteins including P53, CDK6, and MAPK14.

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Abbreviations

EA:

Ellagic acid

Uro:

Urolithins

KEGG:

Kyoto Encyclopedia of Genes and Genomes

String:

Search Tool for the Retrieval of Interacting Genes/Proteins

TTD:

Therapeutic Target Database

PPIs:

Protein–protein interactions

MINT:

Molecular interaction

DIP:

Database of Interacting Proteins

PID:

Pathway Interaction Database

PDB:

Protein Data Bank

IHC:

Immunohistochemistry

GO:

Gene ontology

GAD:

Genetic Association Database

DAVID:

Database for Annotation, Visualization, and Integrated Discovery

GEO:

Gene Expression Omnibus

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Acknowledgements

We gratefully acknowledge the contribution of Ferdowsi University of Mashhad to provide this wonderful chance and good services to perform this study.

Funding

This work was supported by the Ferdowsi University of Mashhad [grant numbers 50828].

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Correspondence to Maryam M. Matin.

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Cheshomi, H., Bahrami, A.R. & Matin, M.M. Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action. Mol Divers 25, 333–349 (2021). https://doi.org/10.1007/s11030-020-10101-6

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  • DOI: https://doi.org/10.1007/s11030-020-10101-6

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