title: Antitumoral action of the neurokinin-1 receptor antagonist L-733 060 on human melanoma cell lines.
abstract: Melanoma represents 1% of all cancers and accounts for approximately 65% of skin cancer deaths. At present, effective treatment does not exist. Substance P (SP) is a neuropeptide expressed in invasive malignant melanomas. We studied the in vitro growth inhibitory capacity of the potent and long-acting neurokinin-1 (NK1) receptor antagonist L-733 060 at concentration ranges of 2.5-20 microM, 10-30 microM and 20-50 microM in the melanoma cell lines COLO 858, MEL H0 and COLO 679, respectively. A Coulter counter was used to determine the number of viable cells, and the tetrazolium compound 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4-sulphophenyl)-2H-tetrazolium, inner salt (MTS) colorimetric method was used to evaluate cell proliferation. L-733 060 inhibited the growth of all three cell lines in a dose-dependent manner. The 50% inhibition concentration (IC(50)) was 8.7 microM at 48 h and 7.1 microM at 96 h for COLO 858, 27.5 microM at 24 h and 18.9 microM at 48 h for MEL H0, and 33.8 microM at 30 h and 31.5 microM at 72 h for COLO 679. These findings indicate that the NK1 receptor antagonist L-733 060 acts as an antitumoral agent. This action, shown here for the first time, suggests that the NK1 receptor antagonist L-733 060 could be a promising therapeutic drug in the treatment of the human melanoma.
authors.affiliation: Hospital Infantil Universitario Virgen del Rocío, Sevilla, Spain. mmunoz@cica.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez
authors.forename: Marisa
authors.initials: M
authors.lastname: Rosso
authors.forename: Carmen
authors.initials: C
authors.lastname: Zamarriego
authors.forename: Rosario
authors.initials: R
authors.lastname: Rosso
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine