The anti-migratory effect of curcumin in colorectal cancer involves IKKβ/NF-κB/Snail-mediated EMT inhibition

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, with distant organ metastasis accounting for the majority of fatal outcomes. Epithelial-mesenchymal transition (EMT) plays a central role in enabling tumor cells to acquire migratory and tissue-invasive competence. Within this context, the IκB kinase β (IKKβ)/nuclear factor-kappa B (NF-κB)/Snail signaling cascade has emerged as a key regulatory hub orchestrating EMT-associated gene programs. Curcumin, a plant-derived polyphenolic compound, displays pleiotropic antitumor properties; however, the molecular basis of its capacity to restrain CRC cell motility requires further clarification. Methods: This investigation evaluated the migration-suppressive capacity of curcumin using HCT116 and SW620 CRC cell lines. Half maximal inhibitory concentration (IC50) values were derived from MTT-based cytotoxicity measurements after 48 hours of drug exposure. Cell cycle progression was characterized by flow cytometry, long-term proliferative potential was gauged through clonogenic assays, and motility was quantified using scratch wound and Transwell chamber approaches. Protein-level alterations in EMT-associated molecules [E-cadherin, N-cadherin, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF)] and constituents of the IKKβ/NF-κB/Snail signaling network were examined by immunoblotting. Results: Following 48-h curcumin exposure, IC50 values of 11.8 µM (HCT116) and 19.5 µM (SW620) were obtained. Uniform working concentrations (0, 6, 12 µM for HCT116; 0, 10, 20 µM for SW620) were applied throughout all downstream assays. Curcumin provoked cell cycle arrest and concentration-dependently reduced proliferative capacity, clonogenic survival, and migratory potential. At the protein level, E-cadherin abundance increased while N-cadherin, MMP-2, and VEGF levels declined in a dose-responsive fashion. Mechanistically, curcumin lowered IKKβ expression, attenuated NF-κB p65 phosphorylation, and down-regulated Snail protein. Conclusions: Collectively, these results indicate that curcumin curtails CRC cell migration, at least in part, through suppression of the IKKβ/NF-κB/Snail-driven EMT program, thereby providing a mechanistic rationale for its further preclinical and clinical evaluation as an adjunctive anti-metastatic approach in CRC.