Eugenol against estrogen receptor-positive breast cancer

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 837-851, Sep-Oct 2024. DOI: https://doi.org/10.56499/jppres23.1699_12.5.837 Original Article Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer [Predicción farmacológica en red y análisis de acoplamiento molecular sobre el mecanismo del eugenol como candidato contra el cáncer … Continue reading Eugenol against estrogen receptor-positive breast cancer

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 837-851, Sep-Oct 2024.

DOI: https://doi.org/10.56499/jppres23.1699_12.5.837

Original Article

Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer

[Predicción farmacológica en red y análisis de acoplamiento molecular sobre el mecanismo del eugenol como candidato contra el cáncer de mama con receptores de estrógeno positivos]

Irene Natalia Nesta Sihombing1*, Ade Arsianti2

1Magister Student of Biomedical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

2Department of Medicinal Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

*E-mail: irene.natalia@ui.ac.id

Abstract

Context: Breast cancer therapy currently presents several uncomfortable side effects in patients, including effects on non-malignant tissues, recurrence, and resistance, which restrict their utilization. Consequently, researchers have directed their attention toward studying plant-derived anticancer compounds that exhibit high efficacy and safety profiles. Eugenol, a major component found in clove plants, demonstrates promising potential as a therapeutic agent for both estrogen receptor-positive and estrogen receptor-negative breast cancer.

Aims: To predict the target of eugenol in estrogen receptor–positive breast cancer using network pharmacology and molecular docking analyses.

Methods: Network pharmacology analysis was performed using the Chemical Toxigenomic Database, STITCH, GeneCards, Cytoscape, Enrichr, and Stringdb. Subsequently, molecular docking was performed using protein targets obtained from the RCSB-PDB and analyzed using AutoDock software.

Results: Network pharmacology study and molecular docking revealed the anticancer effect of eugenol against breast cancer estrogen receptor–positive, especially in cancer and apoptotic pathways, by acting on caspase-3 (CASP3), epidermal growth factor receptor (EGFR), and poly [ADP-ribose] polymerase 1 (PARP1) signaling pathways. The docking results between the protein targets and eugenol showed that eugenol has the strongest binding with CASP3 (ligand binding energy: -5.78 kcal/mol), followed by eugenol binding with EGFR (ligand binding energy: -5.58 kcal/mol), and eugenol binding with PARP1 (ligand binding energy: -5.58 kcal/mol).

Conclusions: Eugenol is a potential candidate for breast cancer therapy, especially for apoptosis mediated by CASP3 in breast cancer luminal A.

Keywords: breast cancer; eugenol; KEGG enrichment; molecular docking; network pharmacology.

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Resumen

Contexto: La terapia del cáncer de mama presenta en la actualidad varios efectos secundarios incómodos en las pacientes, como efectos en tejidos no malignos, recurrencia y resistencia, que restringen su utilización. En consecuencia, investigadores han dirigido su atención al estudio de compuestos anticancerígenos de origen vegetal que presentan perfiles de alta eficacia y seguridad. El eugenol, un componente principal que se encuentra en las plantas de clavo, demuestra un potencial prometedor como agente terapéutico para el cáncer de mama con receptores de estrógeno positivos y negativos.

Objetivos: Predecir la diana del eugenol en el cáncer de mama con receptores de estrógeno positivos mediante farmacología de redes y análisis de acoplamiento molecular.

Métodos: El análisis farmacológico en red se realizó utilizando la base de datos Toxigenómica Química, STITCH, GeneCards, Cytoscape, Enrichr y Stringdb. A continuación, se realizó un acoplamiento molecular con las dianas proteicas obtenidas de la RCSB-PDB y se analizaron con el software AutoDock.

Resultados: El estudio de farmacología en red y el acoplamiento molecular revelaron el efecto anticancerígeno del eugenol contra el cáncer de mama receptor de estrógenos positivo, especialmente en las vías del cáncer y la apoptosis, actuando sobre las vías de señalización de la caspasa-3 (CASP3), el receptor del factor de crecimiento epidérmico (EGFR) y la poli [ADP-ribosa] polimerasa 1 (PARP1). Los resultados del acoplamiento entre las proteínas diana y el eugenol mostraron que el eugenol tiene la unión más fuerte con CASP3 (energía de unión del ligando: -5,78 kcal/mol), seguido de la unión del eugenol con EGFR (energía de unión del ligando: -5,58 kcal/mol), y la unión del eugenol con PARP1 (energía de unión del ligando: -5,58 kcal/mol).

Conclusiones: El eugenol es un candidato potencial para la terapia del cáncer de mama, especialmente para la apoptosis mediada por CASP3 en el cáncer de mama luminal A.

Palabras Clave: cáncer de mama; eugenol; acoplamiento molecular; enriquecimiento KEGG; red de farmacología.

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Citation Format: Sihombing INN, Arsianti A (2024) Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer. J Pharm Pharmacogn Res 12(5): 837–851. https://doi.org/10.56499/jppres23.1699_12.5.837
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