title: Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation.
abstract: The human S100A4 protein binds calcium, resulting in a change in its conformation to promote the interaction with its target protein. Human epidermal growth factor (EGF) is the target protein of S100A4 and a critical ligand of the receptor EGFR. The EGF/EGFR system promotes cell survival, differentiation, and growth by activating several signaling pathways. Amlexanox is an anti-inflammatory and anti-allergic drug that is used to treat recurrent aphthous ulcers. In the present study, we determined that amlexanox interacts with S100A4 using heteronuclear single quantum correlation titration. We elucidated the interactions of S100A4 with EGF and amlexanox using fluorescence and nuclear magnetic resonance spectroscopy. We generated two binary models (for the S100A4-EGF and S100A4-amlexanox complexes) and observed that amlexanox and EGF share a similar binding region in mS100A4. We also used a WST-1 assay to investigate the bioactivity of S100A4, EGF, and amlexanox, and found that amlexanox blocks the binding between S100A4 and EGF, and is therefore useful for the development of new anti-proliferation drugs.
authors: Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
authors: Ching Chang
authors: CC
authors: Cho
authors: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors: Ruey-Hwang
authors: RH
authors: Chou
authors: Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
authors: Chin
authors: C
authors: Yu
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D018926:Anti-Allergic Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005453:Fluorescence; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D000071999:S100 Calcium-Binding Protein A4 / Q000378:metabolism*; D015398:Signal Transduction; D014357:Trypsin / Q000737:chemistry
chemical_list: D000631:Aminopyridines; D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D008024:Ligands; D000071999:S100 Calcium-Binding Protein A4; C077591:S100A4 protein, human; D004815:Epidermal Growth Factor; C045742:amlexanox; D014357:Trypsin; D002118:Calcium