Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation.
Amlexanox Blocks the Interaction between S100A4 and Epidermal Growth Factor and Inhibits Cell Proliferation.
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DOI：
10.1371/journal.pone.0161663
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yu C
中科院分区：
文献类型：
--
作者：
Cho CC;Chou RH;Yu C
人类S100A4蛋白与钙结合，导致其构象改变，促进与靶蛋白的相互作用。人表皮生长因子（EGF）是S100A4的靶蛋白，也是EGFR受体的关键配体。EGF/EGFR系统通过激活多种信号通路促进细胞存活、分化和生长。氨lexanox是一种抗炎和抗过敏药物，用于治疗复发性阿弗顿溃疡。在本研究中，我们利用异核单量子相关滴定法确定了氨lexanox与S100A4的相互作用。我们利用荧光和核磁共振光谱分析了S100A4与EGF和氨lexanox的相互作用。我们建立了两个二元模型（S100A4-EGF和S100A4-amlexanox复合物），并观察到amlexanox和EGF在mS100A4中具有相似的结合区域。我们还使用WST-1实验研究了S100A4、EGF和氨lexanox的生物活性，发现氨lexanox阻断了S100A4和EGF之间的结合，因此有助于开发新的抗增殖药物。
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.