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Investigational New Drugs
Published in: Investigational New Drugs 2/2008

01-04-2008 | Preclinical Studies

NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2

Authors: Miguel Muñoz, Marisa Rosso, Francisco J Aguilar, Miguel A González-Moles, Maximino Redondo, Francisco Esteban

Published in: Investigational New Drugs | Issue 2/2008

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Summary

It has been demonstrated that substance P (SP) induces cell proliferation and neurokinin-1 (NK-1) receptor antagonists inhibit growth in several human cancer cell lines, but it is currently unknown whether such actions are exerted on human laryngeal carcinoma cell line HEp-2. In addition, the presence of NK-1 receptor has not been demonstrated in this cell line. We carried out an in vitro study of the growth inhibitory capacity of the NK-1 receptor antagonists L-733,060 and L-732,138 against human laryngeal carcinoma cell line HEp-2. Coulter counter was used to determine viable cell numbers followed by application of the tetrazolium compound MTS. Furthermore, an immunoblot analysis was used to determine the NK-1 receptor, and the 4′,6-diamidino-2-phenylindole (DAPI) method was applied to demonstrate apoptosis of the laryngeal carcinoma cells. We observed the presence of several NK-1 receptors isoforms (34, 46, 58 and 75 kDa). Nanomolar concentrations of SP increased the growth rate of the cell line and micromolar concentrations of L-733,060 and L-732,138 inhibited the growth of the HEp-2 cells in a dose-dependent manner, with and without previous administration of SP. The 50% inhibition concentration values were 21.34 μM and 37.97 (48 h) respectively for HEp-2. NK-1 receptor presence on HEp-2 cells was confirmed by western blotting. DAPI staining revealed the presence of apoptosis following NK-1 receptor antagonists treatment. We demonstrated that NK-1 receptors were present in this laryngeal cancer cell line; these findings demonstrate that SP acts as a mitogen on the human laryngeal carcinoma cell line HEp-2 through the NK-1 receptor, and also indicate that both NK-1 receptors antagonists induced apoptosis of the tumour cells. This new action, reported here for the first time, suggests that the NK-1 receptor is a new and promising target in the treatment of human laryngeal carcinoma.
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Metadata
Title
NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2
Authors
Miguel Muñoz
Marisa Rosso
Francisco J Aguilar
Miguel A González-Moles
Maximino Redondo
Francisco Esteban
Publication date
01-04-2008
Publisher
Springer US
Published in
Investigational New Drugs / Issue 2/2008
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-007-9087-y

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