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Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation

Ching Chang Cho1, Ruey-Hwang Chou2,3, Chin Yu1

  • 1Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.

Plos One
|August 26, 2016
PubMed

Insights

The drug amlexanox binds to the S100A4 protein, blocking the interaction with epidermal growth factor (EGF). This finding suggests amlexanox

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • S100A4 protein binds calcium, altering its conformation to interact with target proteins.
  • Human epidermal growth factor (EGF) is a target of S100A4 and a ligand for the EGF receptor (EGFR), regulating cell growth.
  • Amlexanox is an anti-inflammatory drug used for aphthous ulcers.

Purpose of the Study:

  • To investigate the interaction between amlexanox and S100A4.
  • To elucidate the binding mechanisms of S100A4 with EGF and amlexanox.
  • To assess the potential of amlexanox as an anti-proliferation drug by understanding its effect on the S100A4-EGF interaction.

Main Methods:

  • Heteronuclear single quantum correlation (HSQC) titration to determine amlexanox-S100A4 interaction.
  • Fluorescence and nuclear magnetic resonance (NMR) spectroscopy to study S100A4 interactions with EGF and amlexanox.
  • WST-1 assay to evaluate the bioactivity of S100A4, EGF, and amlexanox.

Main Results:

  • Amlexanox was found to interact with the human S100A4 protein.
  • Both amlexanox and EGF bind to a similar region on S100A4.
  • Amlexanox inhibits the binding between S100A4 and EGF.

Conclusions:

  • Amlexanox shares a binding site with EGF on S100A4.
  • Amlexanox effectively blocks the S100A4-EGF interaction.
  • Amlexanox shows potential for developing novel anti-proliferation therapeutics.

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