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: Miguel Muñoz, Ana Pérez, Marisa Rosso, Carmen Zamarriego, Rosario Rosso
• Journal: Melanoma research (Melanoma Res) Vol. 14 Issue 3 Pg. 183-8 (Jun 2004) ISSN: 0960-8931 [Print] England
• PMID: 15179186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Neurokinin-1 Receptor Antagonists
• Piperidines
• Receptors, Neurokinin-1
• 3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Inhibitory Concentration 50
• Melanoma (metabolism, pathology)
• Neurokinin-1 Receptor Antagonists
• Piperidines (pharmacology)
• Receptors, Neurokinin-1 (metabolism)