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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

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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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Acknowledgements

This work was supported by the Consejería de Innovacion, Ciencia y Empresa of the Junta de Andalucía (CTS-2247, Spain). The technical assistance of Dr. Marisa Rosso is gratefully acknowledged. The authors thank N. Skinner for stylistic revision of the English text and Manuel Sánchez for technical assistance.

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Authors and Affiliations

  1. Research Laboratory on Neuropeptides, Virgen del Rocío University Hospital, Sevilla, Spain

    Miguel Muñoz & Ana González-Ortega

  2. Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Salamanca, Spain

    Rafael Coveñas

  3. Hospital Infantil 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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  2. Ana González-Ortega
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Correspondence to Miguel Muñoz.

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Muñoz, M., González-Ortega, A. & Coveñas, R. 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. Invest New Drugs 30, 529–540 (2012). https://doi.org/10.1007/s10637-010-9594-0

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  • DOI: https://doi.org/10.1007/s10637-010-9594-0

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