The NK-1 receptor is expressed in human leukemia and is involved in the antitumor action of aprepitant and other NK-1 receptor antagonists on acute lymphoblastic leukemia cell lines

Invest New Drugs. 2012 Apr;30(2):529-40. doi: 10.1007/s10637-010-9594-0. Epub 2010 Dec 1.


Substance P and neurokinin-1 (NK-1) receptor antagonists respectively induce cell proliferation and cell inhibition in human cancer cell lines. In acute lymphoblastic leukemia (ALL), substance P is expressed in human blast cells. However, the possible presence of NK-1 receptors in human ALL and the issue of whether the antitumor action of NK-1 receptor antagonists is exerted or not on human ALL (T-ALL BE-13 and B-ALL SD-1 cell lines) remain unknown. An immunoblot analysis was performed and an in vitro study of the cytotoxicity of three NK-1 receptor antagonists (L-733,060, L-732,138, aprepitant) was carried out on both cell lines. NK-1 receptors were found in those cell lines, and both expressed mRNA for this receptor. Using a knockdown method, we demonstrate that NK-1 receptors are involved in the viability of tumor cells. TAC1R cDNA was detected in the ALL cell lines by real-time quantitative RT-PCR. We also observed that the three NK-1 receptor antagonists elicited the inhibition of ALL cell growth; that the specific antitumor action of the NK-1 receptor antagonists occurs through the NK-1 receptor, and that ALL cell death is due to apoptosis. These findings suggest that NK-1 receptor antagonists could be considered as new antitumor drugs for the treatment of human ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Aprepitant
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Child
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Morpholines / pharmacology*
  • Neurokinin-1 Receptor Antagonists*
  • Piperidines / pharmacology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • RNA Interference
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Neurokinin-1 / genetics
  • Receptors, Neurokinin-1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substance P / metabolism
  • Tryptophan / analogs & derivatives*
  • Tryptophan / pharmacology


  • Antineoplastic Agents
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • RNA, Messenger
  • Receptors, Neurokinin-1
  • 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan
  • 3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
  • Aprepitant
  • Substance P
  • Tryptophan