The substance P/neurokinin-1 receptor system in lung cancer: Focus on the antitumor action of neurokinin-1 receptor antagonists

• DOI: 10.1016/j.peptides.2012.09.024
• Publication Date: 2012-09-28T16:00:31Z
• Authors: Miguel Muñoz; Ana González-Ortega; Marisa Rosso; María José Robles...; Andres Carranza; Manuel Vicente Sa...; Rafael Coveñas
• Keywords: 0301 basic medicine; Lung Neoplasms; Dose-Response Relationship, Drug; Morpholines; Tryptophan; Antineoplastic Agents; Apoptosis; Receptors, Neurokinin-1; Substance P; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Neurokinin-1 Receptor Antagonists; Piperidines; Tumor Cells, Cultured; Humans; Drug Screening Assays, Antitumor; Aprepitant; Cell Proliferation

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.