Antitumoural action of L-733,060 on neuroblastoma and glioma cell lines

Arch Ital Biol. 2004 Mar;142(2):105-12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Humans
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Neurokinin-1 Receptor Antagonists
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / antagonists & inhibitors
  • Substance P / metabolism

Substances

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