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

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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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Acknowledgements

The authors thank Ana Gonzalez and Javier Saenz for technical assistance. This work was partially supported by the Consejería de Innovacion, Ciencia y Empresa of the Junta de Andalucia (CTS-2247, Spain).

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Authors and Affiliations

  1. Research Laboratory on Neuropeptides, “Virgen del Rocío“University Children’s Hospital, Sevilla, Spain

    Miguel Muñoz & Marisa Rosso

  2. Hospital Infantil Universitario Virgen del Rocío, Unidad de Cuidados Intensivos Pediátricos, Av. Manuel Siurot s/n, 41013, Sevilla, Spain

    Miguel Muñoz

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  1. Miguel Muñoz
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Correspondence to Miguel Muñoz.

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Muñoz, M., Rosso, M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs 28, 187–193 (2010). https://doi.org/10.1007/s10637-009-9218-8

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