Antitumoural action of L-733,060 on neuroblastoma and glioma cell lines.
We have performed an in vitro study of the growth-inhibitory capacity of the potent and long-acting NK1 receptor antagonist L-733,060, at concentrations ranging from 2.5 microM to 20 microM, against the neuroblastoma cell line SKN-BE(2) and 10 microM to 25 microM for glioma cell line GAMG. Coulter counter was used to determine viable cell numbers, followed by application of the tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)-2H-tetrazolium], inner salt colorimetric method to evaluate cell viability in this cytotoxicity assay. L-733,060 inhibited the growth of the two cell lines studied in a dose-dependent manner. The IC 50 values were 11.6 microM (30h) and 10.2 microM (72h) for SKN-BE(2); and 21.3 microM (48h) and 19.9 microM (96h) for GAMG. These findings indicate that the NK1 receptor antagonist L-733,060 acts as a broad-spectrum antitumoural agent. This new action, reported here for the first time, suggests that the NK1 receptor antagonist L-733,060 could be a promising therapeutic drug for the treatment of human neuroblastoma and human glioma.
Muñoz
M
M
Hospital Infantil Universitario Virgen del Rocío, Sevilla, Spain. mmunoz@cica.es
Pérez
A
A
Coveñas
R
R
Rosso
M
M
Castro
E
E
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P