The direct STAT3 inhibitor 6-ethoxydihydrosanguinarine exhibits anticancer activity in gastric cancer

Signal transducer and activator of transcription 3 (STAT3) plays a key role in promoting tumor malignant progression. Suppression hyperactivated STAT3 signaling has emerged as potential therapeutic strategy for many cancer types. In this study, the effect 6-ethoxydihydrosanguinarine (6-EDS), secondary transformation product formed from dihydrosanguinarine, isolated Macleaya (Papaveraceae), was evaluated gastric (GC). We demonstrated that 6-EDS inhibited survival, migration, invasiveness GC cells vitro . Moreover, phosphorylation transcriptional activity, thus suppressing mRNA expression downstream target genes associated with cells. Molecular docking indicated directly bound SH2 domain STAT3. dynamics simulations suggested binding phosphorylated non-phosphorylated to DNA. Cellular thermal-shift assays microscale thermophoresis further confirmed direct Site-directed mutagenesis S611 residue is critical binding. vivo , decreased growth xenografted nude mice by blocking signaling. These findings 6-EDS, inhibitor, may be potent anticancer candidate therapy.