title: The substance P/neurokinin-1 receptor system in lung cancer: focus on the antitumor action of neurokinin-1 receptor antagonists.
abstract: The last decades have seen no significant progress in extending the survival of lung cancer patients and there is an urgent need to improve current therapies. The substance P (SP)/neurokinin-1 receptor (NK-1R) system plays an important role in the development of cancer: SP and NK-1R antagonists respectively induce cell proliferation and inhibition in human cancer cell lines. No study of the involvement of this system in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells has been carried out in depth. Here, we demonstrate the involvement of the SP/NK-1R system in human H-69 (SCLC) and COR-L23 (NSCLC) cell lines: (1) they express isoforms of the NK-1R and mRNA for the NK-1R; (2) they overexpress the tachykinin 1 gene; (3) the NK-1R is involved in their viability; (4) SP induces their proliferation; (5) NK-1R antagonists (Aprepitant (Emend), L-733,060, L-732,138) inhibit the growth of both cell lines in a concentration-dependent manner; (6) the specific antitumor action of these antagonists against such cells occurs through the NK-1R; and (7) lung cancer cell death is due to apoptosis. We also demonstrate the presence of NK-1Rs and SP in all the human SCLC and NSCLC samples studied. Our findings indicate that the NK-1R may be a promising new target in the treatment of lung cancer and that NK-1R antagonists could be new candidate antitumor drugs in the treatment of SCLC and NSCLC.
authors.affiliation: Research Laboratory on Neuropeptides, Virgen del Rocío University Hospital, Sevilla, Spain. mmunoz@cica.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.forename: Ana
authors.initials: A
authors.lastname: González-Ortega
authors.forename: Marisa
authors.initials: M
authors.lastname: Rosso
authors.forename: María José
authors.initials: MJ
authors.lastname: Robles-Frias
authors.forename: Andres
authors.initials: A
authors.lastname: Carranza
authors.forename: Manuel Vicente
authors.initials: MV
authors.lastname: Salinas-Martín
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077608:Aprepitant; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000235:genetics; D013329:Structure-Activity Relationship; D013373:Substance P / Q000032:analysis / Q000037:antagonists & inhibitors*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
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