A novel isoxazole compound CM2-II-173 inhibits the invasivephenotype of triple-negative breast cancer cells  

作　　者：EUN SOOK KIM SANGHEE KIM AREE MOON 

机构地区：[1]Duksung Innovative Drug Center,College of Pharmacy,Duksung Women’s University,Seoul,03169,Korea [2]College of Pharmacy,Seoul National University,Seoul,08826,Korea

出　　处：《Oncology Research》2023年第6期867-875,共9页肿瘤学研究（英文）

基　　金：supported by the National Research Foundation of Korea(Nos.2016R1A6A1A03007648,2019R1A2C1009773,2018R1A5A2024425,and 2022R1A2C1093335).

摘　　要：Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality.Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lackof effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on theinvasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibitedinvasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness ofMCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 treatment.Activations of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with CM2-II-173.Proliferation and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibitedinvasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect onthe invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated thatCM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, butalso of liver, prostate, and ovarian cancer cells.

关 键 词：MMP-9 Cell invasion Breast cells 

分 类 号：R737.9[医药卫生—肿瘤]