The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug

Invest New Drugs. 2010 Apr;28(2):187-93. doi: 10.1007/s10637-009-9218-8. Epub 2009 Jan 17.


Aprepitant is a selective high-affinity antagonist of human substance P (SP)/Neurokinin-1 (NK-1) receptors. Until now this drug has been used as anxiolytic, antidepressant and antiemetic. It has been demonstrated that SP induces cell proliferation and NK-1 receptor antagonists different to aprepitant inhibit growth in several human cancer cell lines, where NK-1 receptors are overexpressed. The purpose of this study is to demonstrate the antitumor action of aprepitant. We performed an in vitro study of the growth inhibition capacity of the NK-1 receptor antagonist aprepitant against glioma, neuroblastoma, retinoblastoma and pancreas, larynx, gastric and colon carcinomas cell lines. Coulter counter was used to determine viable cell numbers followed by application of the MTS colorimetric method. Furthermore, a DAPI method was applied to demonstrate apoptosis. We have demonstrated: aprepitant at (5-70 microM) concentration elicits growth cell inhibition in a concentration dependent manner in all tumor cell line studied. Maximum inhibition (100%) was observed when the aprepitant was administered at a concentration of > or = 70 microM in all tumor cell lines studied. The specific antitumor action of aprepitant occurs through the NK-1 receptor and tumor cells death was by apoptosis pathway. These findings reported here for the first time indicate that aprepitant is a new and promising broad spectrum antitumor drug in the treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Aprepitant
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Mitogens / pharmacology
  • Morpholines / pharmacology*
  • Neurokinin-1 Receptor Antagonists*
  • Substance P / metabolism


  • Antineoplastic Agents
  • Mitogens
  • Morpholines
  • Neurokinin-1 Receptor Antagonists
  • Aprepitant
  • Substance P