The NK1 receptor is involved in the antitumoural action of L-733,060 and in the mitogenic action of substance P on neuroblastoma and glioma cell lines.
We have carried out an in vitro study to investigate the ability of substance P to activate cell growth and the NK1 receptor antagonist L-733,060 to inhibit cell growth in the SKN-BE(2) neuroblastoma and GAMG glioma cell lines. A 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. Nanomolar concentrations of substance P increased, and micromolar concentrations of L-733,060 inhibited the growth of both cell lines studied, with and without previous administration of substance P. In addition, we have demonstrated by immunoblot analysis that NK1 receptors are present in both cancer cell lines studied here. Thus, this study demonstrates that substance P acts as a mitogen in the SKN-BE(2) neuroblastoma and GAMG glioma cell lines, and that the antitumoural action of L-733,060 on both human cell lines occurs through the NK1 receptor. This action suggests that the NK1 receptor is a new and promising target in the treatment of human neuroblastoma and glioma.
Muñoz
M
M
Hospital Infantil Universitario Virgen del Rocío, Unidad de Cuidados Intensivos Pediátricos, Av. Manuel Siurot s/n, 41013 Sevilla, Spain. mmunoz@cica.es
Rosso
M
M
Pérez
A
A
Coveñas
R
R
Rosso
R
R
Zamarriego
C
C
Piruat
J I
JI
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008934:Mitogens; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P