title: Rhodanine-based PRL-3 inhibitors blocked the migration and invasion of metastatic cancer cells.
abstract: PRL-3, phosphatase of regenerating liver-3, plays a role in cancer progression through its involvement in invasion, migration, metastasis, and angiogenesis. We synthesized rhodanine derivatives, CG-707 and BR-1, which inhibited PRL-3 enzymatic activity with IC50 values of 0.8 μM and 1.1 μM, respectively. CG-707 and BR-1 strongly inhibited the migration and invasion of PRL-3 overexpressing colon cancer cells without exhibiting cytotoxicity. The specificity of the inhibitors on PRL-3 phosphatase activity was confirmed by the phosphorylation recovery of known PRL-3 substrates such as ezrin and cytokeratin 8. The compounds selectively inhibited PRL-3 in comparison with other phosphatases, and CG-707 regulated epithelial-to-mesenchymal transition (EMT) marker proteins. The results of the present study reveal that rhodanine is a specific PRL-3 inhibitor and a good lead molecule for obtaining a selective PRL-3 inhibitor.
authors.affiliation: Laboratory of Chemical Genomics and Biology, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, 125 Gwahakro, Yoosunggu, Daejeon 305-600, Republic of Korea.
authors.forename: Garam
authors.initials: G
authors.lastname: Min
authors.forename: Su-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Hye-Nan
authors.initials: HN
authors.lastname: Kim
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Han
authors.forename: Rhan-Hee
authors.initials: RH
authors.lastname: Lee
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.forename: Dong Cho
authors.initials: DC
authors.lastname: Han
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012236:Rhodanine / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D012236:Rhodanine; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases