10-Hydroxy-2-decenoic acid, a bioactive component of royal jelly, induces p53-Mediated apoptosis in...

The poor prognosis and limited treatment options for cholangiocarcinoma (CCA) continue to drive the search for novel therapeutics with clear mechanisms of action. 10-hydroxy-2-decenoic acid (10-HDA) is a unique bioactive fatty acid isolated from royal jelly, yet its therapeutic potential in CCA is unknown. In this study, we evaluated the anti-CCA properties of 10-HDA across cell-based, computational, transcriptomic, and animal models. Cell viability and clonogenic assays showed that 10-HDA strongly suppressed HUCCT1 and RBE cell growth by triggering extensive apoptosis. We also observed a marked decline in cell migration and invasion; rather than a purely targeted anti-metastatic effect, transcriptomic data suggested this motility loss is tightly linked to the drug's primary cytotoxicity and a parallel disruption of actin cytoskeleton dynamics. Computational predictions initially pointed toward apoptosis networks as primary targets, which was corroborated by our RNA-seq data highlighting a strong enrichment in both general apoptotic and specific TNF signaling pathways. Protein-level validation confirmed a dual-activation mechanism: 10-HDA upregulates the intrinsic p53/Bax axis while simultaneously engaging the extrinsic TNF/Caspase-8 cascade, both converging on Caspase-3 cleavage. These mechanisms translated effectively in vivo, where 10-HDA administration severely restricted xenograft tumor growth in nude mice without noticeable systemic toxicity. These findings identify 10-HDA as a potent, defined natural agent that halts CCA progression by activating comprehensive apoptotic programs.