Cisplatin-Vernonia amygdalina combination on pancreatic cancer


J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 870-880, Sep-Oct 2024. DOI: Original Article Combination of cisplatin and ethyl acetate extract of Vernonia amygdalina Delile induces cell cycle arrest and apoptosis on PANC-1 cells via PI3K/mTOR [Combinación de cisplatino y extracto de acetato de etilo de Vernonia amygdalina Delile induce la detención del … Continue reading Cisplatin-Vernonia amygdalina combination on pancreatic cancer

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 870-880, Sep-Oct 2024.


Original Article

Combination of cisplatin and ethyl acetate extract of Vernonia amygdalina Delile induces cell cycle arrest and apoptosis on PANC-1 cells via PI3K/mTOR

[Combinación de cisplatino y extracto de acetato de etilo de Vernonia amygdalina Delile induce la detención del ciclo celular y la apoptosis en células PANC-1 vía PI3K/mTOR]

Poppy Anjelisa Zaitun Hasibuan1*, Jane Melita Keliat2, Muhammad Fauzan Lubis3

1Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia.

2Department of Pharmaceutical and Food Analysis, Faculty of Vocational, Universitas Sumatera Utara, Medan, 20155, Indonesia.

3Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia.



Context: Vernonia amygdalina Delile (VAD) is known as a potential plant with a wide variety of medicinal properties, including anticancer.

Aims: To evaluate the combination effect of VAD extract with cisplatin (CIS) against PANC-1 cells, focusing on cell cycle arrest and apoptosis activities.

Methods: This study is an experimental study using PANC-1 cells as objects. The phytochemical compounds were analyzed with LC-MS/MS. The cytotoxic activity of extracts and their combinations was determined using the MTT assay method in the PANC-1 cell line. Apoptosis, cell cycle arrest, and PI3K/mTOR profiles were analyzed with flow cytometry. Immunocytochemistry was used to determine Bcl-2, Cyclin D1, and p53 expression.

Results: The phytochemicals found were five compounds with retention times of 8.96, 9.85, 10.52, 12.59, and 10.36. The results of the MTT assay showed that the IC50 values of extract and CIS were 21.83 ± 0.46 µg/mL and 3.02 ± 0.44 µg/mL, respectively. The combination index (CI) value of extract and CIS had a synergistic effect. Combination extract and CIS induced early and late apoptosis, inhibited cell cycle progression on the G1 phase, inhibited Bcl-2 and cyclin D1 expression, induced p53 expression, and inhibited PI3K and mTOR expression.

Conclusions: The combination of extract and CIS showed anticancer activity against PANC-1 cells through induction of apoptosis and cell cycle arrest via inhibition of PI3K and mTOR expressions.

Keywords: apoptosis; cell cycle arrest; cisplatin; herbal medicine; pancreatic cancer.

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Contexto: Vernonia amygdalina Delile (VAD) es conocida como una planta potencial con una amplia variedad de propiedades medicinales, incluyendo anticancerígenas.

Objetivos: Evaluar el efecto combinado del extracto de VAD con cisplatino (CIS) contra las células PANC-1, centrándose en las actividades de detención del ciclo celular y apoptosis.

Métodos: Este estudio es un estudio experimental utilizando células PANC-1 como objetos. El análisis de los compuestos fitoquímicos se llevó a cabo con LC-MS/MS. La actividad citotóxica del extracto y sus combinaciones se determinó mediante el método de ensayo MTT en la línea celular PANC-1. La apoptosis, la detención del ciclo celular y los perfiles PI3K/mTOR se analizaron con citometría de flujo. Se utilizó inmunocitoquímica para determinar la expresión de Bcl-2, ciclina D1 y p53.

Resultados: Los fitoquímicos hallados fueron cinco compuestos con tiempos de retención de 8,96, 9,85, 10,52, 12,59 y 10,36. Los resultados del ensayo MTT mostraron que los valores de IC50 del extracto y del CIS fueron 21,83 ± 0,46 µg/mL y 3,02 ± 0,44 µg/mL, respectivamente. El valor del índice de combinación (IC) del extracto y el CIS tuvo un efecto sinérgico. La combinación de extracto y CIS indujo la apoptosis temprana y tardía, inhibió la progresión del ciclo celular en la fase G1, inhibió la expresión de Bcl-2 y ciclina D1, indujo la expresión de p53 e inhibió la expresión de PI3K y mTOR.

Conclusiones: La combinación de extracto y CIS mostró actividad anticancerígena contra células PANC-1 a través de la inducción de apoptosis y detención del ciclo celular vía inhibición de las expresiones PI3K y mTOR.

Palabras Clave: apoptosis; detención del ciclo celular; cisplatino; fitoterapia; cáncer de páncreas.

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Citation Format: Hasibuan PAZ, Keliat JM, Lubis MF (2024) Combination of cisplatin and ethyl acetate extract of Vernonia amygdalina Delile induces cell cycle arrest and apoptosis on PANC-1 cells via PI3K/mTOR. J Pharm Pharmacogn Res 12(5): 870–880.

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