Induction of apoptotic and anti-proliferative effects in REH cells upon neurokinin-1 receptor inhibition using Aprepitant

authors:

avatar Elham Razani , avatar A. va Safaroghli-Azar , avatar Davood Bashash , *

Koomesh: Vol.20, issue 4; 748-755
published online: March 30, 2018
article type: issue_documents_importer
received: November 08, 2017
accepted: March 01, 2018

how to cite: Razani E, Safaroghli-Azar A V, Bashash D. Induction of apoptotic and anti-proliferative effects in REH cells upon neurokinin-1 receptor inhibition using Aprepitant. koomesh. 2018;20(4):e153022. 

Abstract

Introduction: Following the first description of neurokinin-1 receptor (NK1R) network as a carcinogenic pathway, overwhelming numbers of studies have reported the inappropriate activity of this cascade in a wide assortment of human cancers. On the basis of the principal importance of NK1R in the pathogenesis of acute lymphoblastic leukemia (ALL), it was of great interest to dissect the effect of Aprepitant, a competing non-peptide NK1R antagonist, on REH Pre-B ALL cells. Materials and Methods: To evaluate the anti-leukemic effect of NK1R antagonist, REH cells were exposed to the increasing concentrations of Aprepitant and subsequent cell viability, growth kinetics, and metabolic activity were investigated. Moreover, to underscore whether Aprepitant-induced cytotoxic effect could be attributed to either induction of apoptosis or cell cycle arrest, Annexin-V/PI staining and DNA content analysis were performed. Finally, the transcriptional alterations of apoptosis-related target genes were studied using RQ-PCR. Results: Intrestingly, we found that abrogation of the NK1R signaling pathway exerts cytotoxic and anti-proliferative effects against REH cells, as evidenced by the increased externalization of phosphatidyl serine (PS), elevated G1 cell population, and decreased number of inhibitor-treated viable cells. In addition, our results also suggested that Aprepitant-induced apoptotic cell death in REH cells is mediated, at least partially, through shifting the ratio of death promoters to death repressors via alteration of Bax and Bcl2 expression. Conclusion: This study highlighted the potent efficacy of Aprepitant in Pre-B ALL cells and shed light on pro-apoptotic property of this inhibitor.  

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