Sisyrinchium palmifolium effects on colitis-associated colon cancer

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 595-604, July-August 2022.

Original Article

Effect of 1,4-naphthoquinone from Sisyrinchium palmifolium L. extract on in vivo Ki-67 expression and in silico CDK1, CDK2, CDK4 on colitis-associated colon cancer

[Efecto de la 1,4-naftoquinona del extracto de Sisyrinchium palmifolium L. sobre la expresión de Ki-67 in vivo y CDK1, CDK2, CDK4 in silico en el cáncer de colon asociado a colitis]

Roihatul Muti’ah1, Agustina T. Endharti2,3, Muhammad F. Wafi4*

1Departement of Pharmacy, Faculty of Medical and Health Sciences, Maulana Malik Ibrahim State Islamic University of Malang, Indonesia.

2Department of Parasitology, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia.

3Biomedical Central Laboratory, Faculty of Medicine, Brawijaya University, Indonesia.

4Master Program in Biomedical Science, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia.

*E-mail: farid_wafi@student.ub.ac.id, dr.faridwafi@gmail.com

Abstract

Context: Medicinal plants can be used as an option for the prevention and reduction of cancer cell resistance and its side effects. Sisyrinchium palmifolium L. is thought to have anti-cancer activity with a compound content of 1,4-naphthoquinone.

Aims: To determine the effect of S. palmifolium extract (SPE) with the main compound 1,4-naphthoquinone on Ki-67 expression by in vivo, and CDK1, CDK2, and CDK4 activity by in silico in colonic epithelial cells of BALB/ c mice induced by azoxymethane (AOM) dextran sodium sulfate (DSS).

Methods: Dayak onion (S. palmifolium) was extracted using 96% ethanol as a solvent. The S. palmifolium extract was then made into tablet form by the wet granulation method. Mice that had been induced with AOM-DSS were given S. palmifolium extract therapy. Twenty samples were used, which were divided into five groups. Mice colon tissue was assessed using Ki-67 immunohistochemistry. This study also used the in silico method to see the effect of 1,4-naphthoquinone compounds from S. palmifolium extract on the expression of CDK1, CDK2 and CDK4 with PDB codes 6GU6, 6GUC, and 1GIH.

Results: Ki-67 expression values were 26 ± 6.51 cells at low dosages, 15 ± 1.73 cells at moderate doses, and 11 ± 1.04 cells at high doses. Between the test groups, there was a statistical differences (p<0.05) with the Post Hoc Mann-Whitney test. At the 6GUC receptor, the mean rerank score of the 1,4-naphtoquinone molecule, which was closest to the native ligand, was -54.6572 ± 2.2722 and -90.5455 ± 1.6524kcal/mole. The steric bond on the amino acid lys 33 (A), which exclusively occurs at the 6GUC receptor, was the only commonality of contact.

Conclusions: 1,4-Naphthoquinone from Sisyrinchium palmifolium L. extract could decrease Ki-67 expression by in vivo, which cloud induce a decrease in epithelial cells proliferation in colon cancer, but has no potential as an inhibitor activity of CDK1, CDK2, and CDK4 by in silico.

Keywords: Dayak onion; immunohistochemistry; 1,4-naphthoquinone.

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Resumen

Contexto: Las plantas medicinales pueden usarse como una opción para la prevención y reducción de la resistencia de las células cancerosas y sus efectos secundarios. Se cree que Sisyrinchium palmifolium L. tiene actividad anticancerígena con un contenido compuesto de 1,4-naftoquinona.

Objetivos: Determinar el efecto del extracto de S. palmifolium (SPE) con el compuesto principal 1,4-naftoquinona sobre la expresión de Ki-67 in vivo y la actividad de CDK1, CDK2 y CDK4 in silico en células epiteliales colónicas de ratones BALB/c inducida por azoximetano (AOM) dextrano sulfato de sodio (DSS).

Métodos: La cebolla de Dayak (S. palmifolium) se extrajo usando etanol al 96% como solvente. Luego, el extracto de S. palmifolium se transformó en forma de tableta mediante el método de granulación en húmedo. Los ratones que habían sido inducidos con AOM DSS recibieron terapia con extracto de S. palmifolium. Se utilizaron veinte muestras, las cuales se dividieron en cinco grupos. El tejido de colon de ratones se evaluó usando inmunohistoquímica Ki-67. Este estudio también usó el método in silico para ver el efecto de los compuestos de 1,4-naftoquinona del extracto de S. palmifolium sobre la expresión de CDK1, CDK2 y CDK4 con los códigos PDB 6GU6, 6GUC y 1GIH.

Resultados: Los valores de expresión de Ki-67 fueron 26 ± 6,51 células a dosis bajas, 15 ± 1,73 células a dosis moderadas y 11 ± 1,04 células a dosis altas. Entre los grupos de prueba, hubo diferencias estadísticas (p<0,05) con la prueba Post Hoc Mann-Whitney. En el receptor 6GUC, la puntuación de reclasificación media de la molécula de 1,4-naftoquinona, que era la más cercana al ligando nativo, fue -54,6572 ± 2,2722 y -90,5455 ± 1,6524 kcal/mol. El enlace estérico en el aminoácido lys 33 (A), que ocurre exclusivamente en el receptor 6GUC, fue el único elemento común del contacto.

Conclusiones: La 1,4-naftoquinona del extracto de Sisyrinchium palmifolium L. podría disminuir la expresión de Ki-67 in vivo, lo que induce una disminución en la proliferación de células epiteliales en el cáncer de colon, pero no tiene potencial como inhibidor de la actividad de CDK1, CDK2 y CDK4 in silico.

Palabras Clave: cebolla Dayak; inmunohistoquímica; 1,4-naftoquinona.

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Citation Format: Muti’ah R, Endharti AT, Wafi MF (2022) Inhibition of Sisyrinchium palmifolium L. ethanolic extract on CDK1, CDK2, CDK4 and Ki-67 expression on colitis-associated colon cancer. J Pharm Pharmacogn Res 10(4): 595–604.
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