Anti-Cancer Effect of Aprepitant on Nb4 Leukemic Cells

Abstract

BACKGROUND AND OBJECTIVE: Genetic studies have demonstrated that the neurokini-1 Receptor (NK1R (is frequently involved in the pathogenesis of wide assortment of human malignancies, including acute promyelocytic leukemia (APL). The activity of this pathway in leukemic cells results in an excessive cell proliferation and evade from apoptosis. In this study, we aimed to investigate the effect of Aprepitant (NK1R antagonist) on the survival rate of APL cells. METHODS: This experimental study is conducted on APL-derived NB4 cells (Institute Pasteur). To determine the anti-tumor effect of Aprepitant, NB4 cells were divided into 6 groups: control and 1-, 2-, 3-, 4- and 5 µM-drug treated groups. Then the cell viability, metabolic activity, induction of apoptosis and transcriptional alteration of Bax and Bcl-2 genes were investigated after 24 and 36 h treatment using trypan blue assay, MTT assay, Annexin-V/PI staining and RQ-PCR analysis, respectively. FINDINGS: 36 h treatment with the highest concentration of Aprepitant (5 µM) resulted in an approximately 50% reduction in the viability (assessed by trypan blue) and metabolic activity (assessed by MTT assay) of NB4 cells (p<0.001) in comparison with control group. Moreover, Aprepitant is able to increase the proportion apoptotic cells from 1.4% in control group to 10.6% in 5 µM drug-treated cells though up-regulating Bax/Bcl-2 molecular ratio (p≤0.05). CONCLUSION: Aprepitant exerted both cytotoxic and anti-proliferative effects in NB4 cells