Cetuximab and Volvariella volvacea ethanol extract in colorectal cancer

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J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1129-1142, Nov-Dec 2024. DOI: https://doi.org/10.56499/jppres23.1895_12.6.1129 Original Article Enhanced anticancer effect of cetuximab combined with ethanol extract of Volvariella volvacea in colorectal cancer targeted TOP2A and PPARγ [Efecto anticancerígeno mejorado de cetuximab combinado con extracto etanólico de Volvariella volvacea en el cáncer colorrectal dirigido a TOP2A y … Continue reading Cetuximab and Volvariella volvacea ethanol extract in colorectal cancer

J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1129-1142, Nov-Dec 2024.

DOI: https://doi.org/10.56499/jppres23.1895_12.6.1129

Original Article

Enhanced anticancer effect of cetuximab combined with ethanol extract of Volvariella volvacea in colorectal cancer targeted TOP2A and PPARγ

[Efecto anticancerígeno mejorado de cetuximab combinado con extracto etanólico de Volvariella volvacea en el cáncer colorrectal dirigido a TOP2A y PPARγ]

Sofy Permana1*, Elsafira A. Nabilahasna2, Fairuz A. Meilany2, Silvi Zakiyatul Ilmiyah2, Edwin Widodo3, Eviana Norahmawati4, Yoshiyuki Kawamoto5, Heni Endrawati6, Agustina T. Endharti6,7

1Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Indonesia.

2Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya Malang, Indonesia.

3Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Indonesia.

4Department of Biomedical Sciences, College of Life and Health Sciences. Chubu University, Japan.

5Department of Pathology Anatomy, Faculty of Medicine, Universitas Brawijaya, Indonesia.

6Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Indonesia.

7Biomedical Central Laboratories, Faculty of Medicine, Universitas Brawijaya Malang, Indonesia.

*E-mail: sofy-bio@ub.ac.id

Abstract

Context: Colorectal cancer (CRC) is a major global health concern as innovative therapeutic strategies to enhance treatment outcomes. This study investigates the therapeutic potential of the ethanol extract derived from Volvariella volvacea in combination with cetuximab for CRC.

Aims: To evaluate the inhibition of topoisomerase II alpha (TOP2A) and include the peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of cell growth and differentiation.

Methods: The method used computational modeling and molecular docking to assess the binding affinities and interactions between the bioactive components, cetuximab, TOP2A, and PPARγ. In vitro experiments were conducted using CRC cell lines. Cells were treated with cetuximab alone or in combination with V. volvacea extract. Cell viability and immunofluorescence were conducted to evaluate the effect of combination therapy on TOP2A and PPARγ.

Results: The results unveiled compelling binding interactions, suggesting the potential for dual targeting of TOP2A and PPARγ. The results demonstrated a reduction in cell viability, downregulation of TOP2A, and modulation of PPARγ. These findings indicate the potential of V. volvacea extract as an adjuvant therapy to cetuximab in CRC. Targeting both TOP2A and PPARγ enhances the efficacy of CRC treatment.

Conclusions: Moreover, it highlights the importance of harnessing natural compounds and molecular insights to develop innovative combinatorial therapies for complex diseases like CRC.

Keywords: cetuximab; colorectal cancer; PPARγ; TOP2A; Volvariella volvacea.

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Resumen

Contexto: El cáncer colorrectal (CCR) es un importante problema de salud mundial debido a las estrategias terapéuticas innovadoras para mejorar los resultados del tratamiento. Este estudio investiga el potencial terapéutico del extracto de etanol derivado de Volvariella volvacea en combinación con cetuximab para el CCR.

Objetivos: Evaluar la inhibición de la topoisomerasa II alfa (TOP2A) e incluir el receptor gamma activado por proliferador de peroxisomas (PPARγ), un regulador clave del crecimiento y diferenciación celular.

Métodos: Se utilizó modelado computacional y acoplamiento molecular para evaluar las afinidades de unión y las interacciones entre los componentes bioactivos, cetuximab, TOP2A y PPARγ. Se realizaron experimentos in vitro utilizando líneas celulares CRC. Las células se trataron con cetuximab solo o en combinación con extracto de V. volvacea. Se realizaron viabilidad celular e inmunofluorescencia para evaluar el efecto de la terapia combinada sobre TOP2A y PPARγ.

Resultados: Los resultados revelaron interacciones de unión convincentes, lo que sugiere el potencial de una doble orientación de TOP2A y PPARγ. Los resultados demostraron una reducción en la viabilidad celular, una regulación negativa de TOP2A y una modulación de PPARγ. Estos hallazgos indican el potencial del extracto de V. volvacea como terapia adyuvante del cetuximab en el CCR. Dirigirse tanto a TOP2A como a PPARγ mejora la eficacia del tratamiento del CCR.

Conclusiones: Además, destaca la importancia de aprovechar los compuestos naturales y los conocimientos moleculares para desarrollar terapias combinatorias innovadoras para enfermedades complejas como el CCR.

Palabras Clave: cáncer colonrectal; cetuximab; PPARγ; TOP2A; Volvariella volvacea.

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Citation Format: Permana S, Nabilasna ER, Meilaniy FA, Ilmiyah SZ, Widodo E, Norahmawati E, Kawamoto Y, Endrawati H, Endharti AT (2024) Enhanced anticancer effect of cetuximab combined with ethanol extract of Volvariella volvacea in colorectal cancer targeted TOP2A and PPARγ. J Pharm Pharmacogn Res 12(6): 1129–1142. https://doi.org/10.56499/jppres23.1895_12.6.1129
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