WLJP-025p, a pectic polysaccharide from Lonicera japonica Thunb., suppresses proliferation and cellular respiration in IHH-4 thyroid cancer cells through a Gal-3-associated FAK/SRC signaling pathway.

Lonicera japonica polysaccharides have been reported to possess anti-tumor potential, but their effects and mechanisms in thyroid cancer remain insufficiently defined. In this study, an acidic pectic polysaccharide, WLJP-025p (average molecular weight 23 kDa; purity 93.7%), was screened for selective anti-proliferative activity against IHH-4 papillary thyroid cancer cells. Based on the carbohydrate-recognition properties of galectin proteins and bioinformatics analysis of thyroid cancer datasets, Gal-3 was selected as a candidate WLJP-025p-interacting protein. Fluorescence spectroscopy and biolayer interferometry further supported a biochemical interaction between WLJP-025p and Gal-3. Functionally, WLJP-025p suppressed IHH-4 cells proliferation and migration, reduced Gal-3/FAK/SRC-associated signaling, and impaired glycolysis and mitochondrial respiration-related functional readouts as indicated by ECAR and OCR assays. In a nude mouse xenograft model, intratumoral WLJP-025p administration reduced tumor growth and downregulated Gal-3/FAK/SRC-associated protein signals in tumor tissue. These findings suggest that WLJP-025p suppresses IHH-4 thyroid cancer cell proliferation at least partly through a Gal-3-associated FAK/SRC signaling pathway and provide proof-of-concept evidence for further development of L. japonica polysaccharides as anti-tumor macromolecules.