Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells
| Autor: | Opa Vajragupta, Ikuo Saiki, Alaa Refaat, Sherif Abdelhamed, Chawannuch Mudjupa, Satoru Yokoyama |
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| Rok vydání: | 2015 |
| Předmět: |
General Immunology and Microbiology
Chemistry medicine.drug_class General Neuroscience Health Toxicology and Mutagenesis Biomedical Engineering General Medicine Pharmacology medicine.disease Lapatinib Metastatic breast cancer General Biochemistry Genetics and Molecular Biology Tyrosine-kinase inhibitor Gefitinib Artificial Intelligence Cancer cell Cancer research medicine General Pharmacology Toxicology and Pharmaceutics skin and connective tissue diseases General Agricultural and Biological Sciences Lung cancer Triple-negative breast cancer medicine.drug EGFR inhibitors |
| Zdroj: | Journal of Applied Biomedicine. 13:305-317 |
| ISSN: | 1214-0287 1214-021X |
| DOI: | 10.1016/j.jab.2015.05.001 |
| Popis: | 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 IC 50 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 IC 50 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. |
| Databáze: | OpenAIRE |
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