Tectochrysin, a propolis-associated flavone, suppresses colorectal cancer progression and modulates ERBB4-associated signalling.

Tectochrysin is a propolis-associated methoxylated flavone with reported anticancer activity, but its actions in colorectal cancer (CRC) remain incompletely defined. In CRC mouse models, tectochrysin reduced orthotopic tumor-associated bioluminescence and the numbers of histologically identified lung and liver metastatic nodules. In vitro, tectochrysin reduced CRC-cell viability, EdU incorporation, spheroid formation, wound closure, Matrigel invasion, and tumor-cell-conditioned HUVEC network formation. In orthotopic tumors, tectochrysin was associated with lower LGR5, EpCAM, VEGFA, and VEGFR1 immunoreactivity and lower CD31-positive microvessel density. Exploratory transcriptomic analysis prioritised ERBB4-associated signalling for follow-up. Molecular docking predicted tectochrysin poses within the ERBB4 kinase pocket, and surface plasmon resonance provided biophysical evidence of an interaction with immobilised ERBB4 under the assay conditions. Tectochrysin reduced selected ERBB4-AKT/ERK signalling readouts, and ERBB4 gain- and loss-of-function modified selected signalling and EMT-associated responses. Although liver weight increased in the T10 metastasis cohort, endpoint serum ALT and AST in that cohort and complementary non-tumour liver histology in an orthotopic cohort did not indicate overt hepatic injury under the tested regimen. Collectively, these findings support ERBB4 as a contributor to tectochrysin-responsive signalling while emphasising the need for orthogonal target-validation, pharmacokinetic, and bioavailability studies before nutritional or translational relevance can be established.