ABSTRACT

Many malignancies originate from prolonged inflammation where the tumor microenvironment, which is predominantly regulated by inflammatory cells, is a crucial player in the neoplastic process, supporting proliferation and migration. Phosphodiesterase-4 inhibitors and amygdalin analogs showed great potential to treat inflammatory diseases such as psoriasis and become challenging for hindering malignant ascites. Ascites was induced by intraperitoneal inoculation of Ehrlich ascites carcinoma (EAC) in mice then after 14 days mice were distributed into four groups; the positive control, group treated with cisplatin, and two groups received cisplatin in combination with acefylline or amygdalin for seven days. Flow cytometry was used to evaluate cell cycle phases and expression of cyclin B1 (CDK-B1), p53, and p21 as cell cycle regulators. Proliferation was assessed by Ki-67 expression and proliferation index was estimated. Apoptosis was determined by analysis of the pro-apoptotic Bax and the anti-apoptotic Bcl-2 expression. Both acefylline and amygdalin combination with cisplatin showed a reduction in Ki-67 expression and arrested the cell cycle. Amygdalin treatment showed a significant reduction in S-phase and proliferation index. This combination also restored the cell’s apoptotic ability proved by the apoptosis index and increased p53, p21, and Bcl-2 expression while reducing Bax expression in ascites. Results showed a distinct effect of amygdaline associated with a significant reduction in the ascites burden with markedly decreased proliferation and induced apoptosis. These findings provide a basis for the theory that anti-inflammatory agents could be used efficiently to delay tumor growth and hinder cell cycle by their effective antiproliferative activity. Keywords: Acefylline, p21, amygdalin, flow cytometry, Ki-67, proliferation
Publication date: 01/04/2024

https://ijbpas.com/pdf/2024/April/MS_IJBPAS_2024_7978.pdf

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https://doi.org/10.31032/IJBPAS/2024/13.4.7978