Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

Journal of Applied Biomedicine

关键词: CAcaffeic acid;    CAPEcaffeic acid phenethyl ester;    EGFRepidermal growth factor receptor;    RTKreceptor tyrosine kinase;    TNBCtriple-negative breast cancer;    Caffeic acid derivatives;    EGFR inhibitor;    Triple-negative breast cancer;    Non-small cell lung cancer;    Molecular modeling;   

DOI  :  10.1016/j.jab.2015.05.001

学科分类：医学（综合）

来源: Elsevier

【 摘 要 】

A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer H460 cells with IC50 values of 8.96 μM and 12.98 μM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC50 2.34 μM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

【 授权许可】

Unknown