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Description

A cell-permeable isoxazolocarboxamide compound that enhances the E-cadherin protein level in lung squamous cell carcinoma H520 and colorectal adenocarcinoma SW620 cells (6.3- and 10-fold, respectively, 10 µ,M for 24 h) in a dose-dependent manner (EC50 = 1.25 and 2.13 µ,M, respectively), resulting in an effective culture invasiveness reduction (by ~50% in SW620 invasion assays). The observed cellular E-cadherin protein upregulation correlates well with an increase in both cellular E-cadherin gene CHD1 transcription (10.2-fold increase in SW620 by RNA-Seq analysis,10 µ,M for 24 h) and histone H4 Lys9 acetylation (19- and 57-fold enhancement in H529 and SW620 cells, respectively, 10 µ,M for 24 h), although evidence indicates no direct inhibition of HDACs 1-11 activity by the compound and other cellular factors involved in histone acetylation regulation are the likely candidates as the direct drug target(s).