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01-04-2012 | PRECLINICAL STUDIES

The NK-1 receptor is expressed in human leukemia and is involved in the antitumor action of aprepitant and other NK-1 receptor antagonists on acute lymphoblastic leukemia cell lines

Authors: Miguel Muñoz, Ana González-Ortega, Rafael Coveñas

Published in: Investigational New Drugs | Issue 2/2012

Summary

Substance P and neurokinin-1 (NK-1) receptor antagonists respectively induce cell proliferation and cell inhibition in human cancer cell lines. In acute lymphoblastic leukemia (ALL), substance P is expressed in human blast cells. However, the possible presence of NK-1 receptors in human ALL and the issue of whether the antitumor action of NK-1 receptor antagonists is exerted or not on human ALL (T-ALL BE-13 and B-ALL SD-1 cell lines) remain unknown. An immunoblot analysis was performed and an in vitro study of the cytotoxicity of three NK-1 receptor antagonists (L-733,060, L-732,138, aprepitant) was carried out on both cell lines. NK-1 receptors were found in those cell lines, and both expressed mRNA for this receptor. Using a knockdown method, we demonstrate that NK-1 receptors are involved in the viability of tumor cells. TAC1R cDNA was detected in the ALL cell lines by real-time quantitative RT-PCR. We also observed that the three NK-1 receptor antagonists elicited the inhibition of ALL cell growth; that the specific antitumor action of the NK-1 receptor antagonists occurs through the NK-1 receptor, and that ALL cell death is due to apoptosis. These findings suggest that NK-1 receptor antagonists could be considered as new antitumor drugs for the treatment of human ALL.

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Title: The NK-1 receptor is expressed in human leukemia and is involved in the antitumor action of aprepitant and other NK-1 receptor antagonists on acute lymphoblastic leukemia cell lines
Authors: Miguel Muñoz
Ana González-Ortega
Rafael Coveñas
Publication date: 01-04-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 2/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-010-9594-0

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