The neurokinin-1 receptor antagonist aprepitant is a promising candidate for the treatment of breast cancer.

Abstract

The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the drug aprepitant on BC cells is currently unknown. We show the involvement of this system in human BC cell lines: i) these cells express mRNA for the NK-1 receptor; ii) they overexpress NK-1 receptors; iii) the NK-1 receptor is involved in their viability; iv) SP induces their proliferation; v) NK-1 receptor antagonists block SP-induced mitogen stimulation of these cells; vi) the specific antitumor action of such antagonists on these cells occurs through the NK-1 receptor; and vii) BC cell death is due to apoptosis. We also found NK-1 receptors and SP in all human BC samples studied. The NK-1 receptor may be a promising target in the treatment of BC and NK-1 receptor antagonists could be candidates as a new antitumor drug in the treatment of BC.

• Authors: Miguel Muñoz, Ana González-Ortega, Manuel Vicente Salinas-Martín, Andrés Carranza, Susana Garcia-Recio, Vanessa Almendro, Rafael Coveñas
• Journal: International journal of oncology (Int J Oncol) Vol. 45 Issue 4 Pg. 1658-72 (Oct 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25175857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Morpholines
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Receptors, Neurokinin-1
• 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
• 3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
• Aprepitant
• Substance P
• Tryptophan

Topics

• Antineoplastic Agents (pharmacology)
• Aprepitant
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Humans
• MCF-7 Cells
• Morpholines (pharmacology)
• Neurokinin-1 Receptor Antagonists (pharmacology)
• Piperidines (pharmacology)
• Receptors, Neurokinin-1 (genetics, metabolism)
• Substance P (metabolism)
• Tryptophan (analogs & derivatives, pharmacology)