title: 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.affiliation: Virgen del Rocío University Hospital, Research Laboratory on Neuropeptides, Sevilla, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Virgen del Rocío University Hospital, Research Laboratory on Neuropeptides, Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Ortega
authors.affiliation: Deparment of Pathology, Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Manuel Vicente
authors.initials: MV
authors.lastname: Salinas-Martín
authors.affiliation: Virgen del Rocío University Hospital, Research Laboratory on Neuropeptides, Sevilla, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Carranza
authors.affiliation: Department of Medical Oncology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Garcia-Recio
authors.affiliation: Department of Medical Oncology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Almendro
authors.affiliation: Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), Salamanca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077608:Aprepitant; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D000077608:Aprepitant; D013373:Substance P; D014364:Tryptophan