10-Hydroxy-2-decenoic Acid Suppresses Colorectal Cancer Progression by Inhibiting Wnt/β-Catenin Signaling and...

Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, and advanced disease continues to show poor prognosis due to therapeutic limitations and drug resistance. Royal jelly (RJ), a natural functional food and dietary supplement, contains 10-hydroxy-2-decenoic acid (10-HDA), a bioactive fatty acid unique to RJ with demonstrated anticancer potential. This study evaluated the anti-CRC effects and underlying mechanisms of 10-HDA through cellular, animal, and transcriptomic approaches. 10-HDA markedly suppressed CRC cell viability with IC₅₀ of 2.07 mM and 3.49 mM against HCT 116 and HT-29 cells, respectively, reduced gap closure by 29.30%, elevated intracellular reactive oxygen species (ROS), and attenuated xenograft tumor growth dose-dependently. Preliminary safety evaluation suggested that 10-HDA was well tolerated under the tested conditions, with no significant changes in body weight, serum AST, ALT, or ALP levels, or organ histology. Transcriptomic analysis showed significant enrichment of apoptosis and Wnt/β-catenin pathways. Molecular assessments indicated that 10-HDA was associated with alterations in apoptosis-related features, including increased caspase-3 activity, changes in Bcl-2 family proteins, and elevated ROS levels, as well as with modulation of the Wnt/β-catenin signaling pathway. These changes were consistent with enhanced β-catenin degradation and reduced nuclear translocation. It suggests that Wnt/β-catenin may be involved in the anti-CRC effects of 10-HDA. This study mechanistically clarifies the anti-CRC activity of 10-HDA as a natural food-derived bioactive compound, suggesting its therapeutic potential for Wnt/β-catenin dysregulated CRC.