| Summary: | Ziyu Liu,1,2 Leilei Huang,3,4 Liwei Sun,1 Hui Nie,3,4 Yuqi Liang,1,2 Jinwen Huang,3,4 Fanhong Wu,3,4 Xin Hu1 1The Laboratory of Cancer Biology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, School of Life Science, Jilin University, Changchun, Jilin, People’s Republic of China; 3Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai, People’s Republic of China; 4Department of Pharmaceutical Engineering, School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, People’s Republic of ChinaCorrespondence: Xin Hu; Fanhong Wu Email huxin@jlu.edu.cn; wfh@sit.edu.cnPurpose: Erianin is a small chemical compound extracted from Dendrobium chrysotoxum and has excellent antineoplastic effects against a variety of cancers. Combretastatin A-4 (CA4) is the most effective member of natural phenolic stilbene compounds isolated from the African willow tree Combretum caffrum. Ecust004 (Chemical Formula: C18H21NO7S) is a drug candidate optimized from structure–activity relationship studies of the sulfamate derivatives of Erianin and CA4, which has better bioavailability and pharmacokinetic profiles than Erianin and CA4.Methods: To investigate the antitumor activity of Ecust004 in different types of breast cancer cells, MDA-MB-231 and MCF7 cells were treated with Ecust004. MTT and CCK8 were used to determine the effects of Ecust004 on cell proliferation. Wound-healing and Transwell assays were used to evaluate the migration and invasion level of cells treated with Ecust004. The expression of genes and proteins associated with epithelial–mesenchymal transition was detected by RT-PCR and Western blotting. In vivo studies further clarified the functional effects of Ecust004.Results: Ecust004 treatment decreased the growth and proliferation of MDA-MB-231 and MCF7 cells at a lower dosage than Erianin. In addition, compared to Erianin and CA4, Ecust004 can better inhibit the invasion and migration of MDA-MB-231 and MCF7 cells. Accordingly, the expression of genes associated with epithelial–mesenchymal transition, such as E-cadherin and vinculin, was increased. Finally, compared with Erianin and CA4, Ecust004 exhibited a better anti-tumor activity in vivo.Conclusion: Ecust004 inhibits the proliferation, invasion, and migration of breast cancer cells, and therefore represents a potential agent for development as an antitumor drug.Keywords: Ecust004, Erianin, breast cancer, EMT
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