SNU523 Inhibits Pancreatic Cancer through the Dual Suppression of STAT3 and MEK Signaling Pathways

Abstract Pancreatic cancer represents one of the most lethal cancers, characterized by poor survival rates and persistent therapeutic resistance. In this study, we investigated the anticancer potential and underlying mechanism of SNU523 (8-O-demethyl-9,11-didechloropestalone), a compound isolated from the marine-derived fungus Pestalotiopsis neglecta. SNU523 exhibited potent antiproliferative effects, reduced colony formation in PDAC cells, and suppressed tumor growth in a xenograft model. SNU523 demonstrated dual inhibitory activity against the STAT3 and MEK signaling pathways, suggesting the potential for overcoming therapeutic resistance driven by the inverse interplay between these cascades. This dual suppression may be attributed to its modulatory effects on the epidermal growth factor receptor (EGFR) protein and mRNA levels. Taken together, these findings suggest that SNU523 represents a highly promising candidate for targeted therapy against pancreatic cancer, and it merits extensive investigation in both preclinical and clinical settings.