In Silico and In Vitro Anticancer Activities of Punica granatum L Peel Ethanolic Extract Against Topoisomerase II Alpha in HeLa and cMM/IPB-B4 Cell Lines

Articles in Press

Document Type : Original Articles

Authors

1 Division of Veterinary Pathology , School of Veterinary Medicine and Biomedical Sciences, IPB University

2 Animal Biomedical Science Study Program, School of Veterinary Medicine and Biomedical Sciences, IPB University

3 Division of Veterinary Pharmacology, School of Veterinary Medicine and Biomedical Sciences, IPB University

4 Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University

5 School of Veterinary Medicine and Biomedical Sciences, IPB University

10.22059/ijvm.2025.400986.1005882

Abstract

Background: Cancer remains a leading cause of death globally, and the development of new, effective, and less toxic treatments from natural sources is a key area of research. Pomegranate peel, a rich source of bioactive compounds, has shown promise as a natural anticancer agent.
Objectives: This study examines the anti-proliferative properties of pomegranate peel ethanolic extract against cMM/IPB-B4 and HeLa cells. The study also utilized in silico approaches to explore the potential inhibitory activities of the pomegranate’s major compounds, such as punicalagin, ellagic acid, and gallic acid, against Topoisomerase IIα.
Methods: An ethanolic extract of pomegranate peel was prepared using maceration method. In vitro anti-proliferative activity was assessed using a cell viability assay on HeLa and cMM/IPB-B4 cells. The IC50 values were determined, and a BSLT was conducted to evaluate toxicity. An in silico analysis using AutoDock Vina, PASS Online, ADMET-AI screening was performed to study the interactions of the compounds with the Topoisomerase IIα enzyme.
Results: The extract demonstrated anti-proliferative effects with IC50 values of 943.43 µg/mL for HeLa cells and 1152.42 µg/mL for cMM/IPB-B4 cells. In silico docking revealed that punicalagin is the best Topoisomerase IIα inhibitor (-7.24 kcal/mol). The ADMET analysis indicated that punicalagin has a moderately safety profile.
Conclusion: Pomegranate peel ethanolic extract exhibits anti-proliferative activity against both HeLa and cMM/IPB-B4 cells. The in silico findings strongly suggest that punicalagin is a key compound contributing to this effect by inhibiting Topoisomerase IIα. These results support the potential of pomegranate peel extract as novel anticancer therapies, especially against cMM/IPB-B4.

Keywords

Iranian Journal of Veterinary Medicine

Articles in Press, Accepted Manuscript
Available Online from 11 November 2025

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