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01-04-2010 | Preclinical Studies

The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug

Authors: Miguel Muñoz, Marisa Rosso

Published in: Investigational New Drugs | Issue 2/2010

Summary

Aprepitant is a selective high-affinity antagonist of human substance P (SP)/Neurokinin-1 (NK-1) receptors. Until now this drug has been used as anxiolytic, antidepressant and antiemetic. It has been demonstrated that SP induces cell proliferation and NK-1 receptor antagonists different to aprepitant inhibit growth in several human cancer cell lines, where NK-1 receptors are overexpressed. The purpose of this study is to demonstrate the antitumor action of aprepitant. We performed an in vitro study of the growth inhibition capacity of the NK-1 receptor antagonist aprepitant against glioma, neuroblastoma, retinoblastoma and pancreas, larynx, gastric and colon carcinomas cell lines. Coulter counter was used to determine viable cell numbers followed by application of the MTS colorimetric method. Furthermore, a DAPI method was applied to demonstrate apoptosis. We have demonstrated: aprepitant at (5–70 μM) concentration elicits growth cell inhibition in a concentration dependent manner in all tumor cell line studied. Maximum inhibition (100%) was observed when the aprepitant was administered at a concentration of ≥70 µM in all tumor cell lines studied. The specific antitumor action of aprepitant occurs through the NK-1 receptor and tumor cells death was by apoptosis pathway. These findings reported here for the first time indicate that aprepitant is a new and promising broad spectrum antitumor drug in the treatment of cancer.

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Title: The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug
Authors: Miguel Muñoz
Marisa Rosso
Publication date: 01-04-2010
Publisher: Springer US
Published in: Investigational New Drugs / Issue 2/2010
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-009-9218-8

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