Stilbene-based strategies for the management of endometriosis: targeting cell adhesion, migration, and ECM-driven invasion

Endometriosis develops when endometrial fragments implant in the peritoneal cavity, overcome structural barriers, or enter through existing tissue injury, leading to the formation of ectopic endometrium-like tissue. This study aimed to investigate the therapeutic potential of resveratrol and its natural analogs in modulating migratory, invasive, and adhesive interactions of endometriotic cells. Adhesion to ECM components, such as collagen I and fibronectin, was assessed by crystal violet staining and showed that stilbenes reduced cell attachment more pronouncedly on fibronectin-coated surfaces. Migration and invasion through Matrigel-coated chambers were dose-dependently suppressed by all compounds, with pterostilbene and piceatannol exerting the most potent inhibitory effects. Expression and secretion of key ECM proteolysis mediators, MMP-2 and TIMP-2, analyzed by qRT-PCR and ELISA, were modulated by stilbene treatment. These findings highlight the potential of resveratrol and its analogs as promising agents for preventing local growth, migration, and invasion of endometriotic cells. • Stilbenes more strongly inhibited cell adhesion to fibronectin than to collagen I. • Stilbenes effectively suppressed 12Z cell migration and invasiveness. • Resveratrol and its analogs modified level of key ECM proteolysis molecules. • Study reveals stilbenes disrupt cell-ECM interaction and invasion in endometriosis.