Elucidating the molecular mechanism of angiogenic activity of sulfate glycosaminoglycan derived from fish swim bladder in human umbilical vein endothelial cells

Fish swim bladders are considered a traditional marine aquatic food that has medicinal and nutritional properties. Sulfate glycosaminoglycans (SBSG) obtained from fish swim bladders may have anti-angiogenic activity. However, the anti-angiogenic activity of SBSG and its mechanism has not been reported. Therefore, the present study investigated the effect of SBSG on angiogenesis and examined molecular pathways in human umbilical vein endothelial cells (HUVECs) using cell viability, chicken chorioallantoic membrane (CAM) assay, tube formation assay, and proteomic analyses. The results demonstrated that the SBSG significantly ( P < 0.05 ) suppressed tube formation in the HUVECs while decreasing vascular density in CAM. Quantitative proteome analysis identified 1474 differentially expressed proteins (DEPs) involved in different molecular pathways. In the bladder cancer pathway, 10 proteins were significantly downregulated [matrix metalloproteinase-9 (MMP-9), epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), fibroblast growth factor receptor 3 (FGFR3), harvey rat sarcoma (H-Ras), rat sarcoma (Ras), mitogen-activated extracellular signal-regulated kinase (MEK), extracellular regulated protein kinases (ERK), receptor tyrosine-protein kinase erbB-2 (ERBB2), and E -Cadherin (E-cad)], whereas 2 proteins were significantly upregulated [thrombospondin-1 (TSP-1) and E-cad]. Notably, SBSG was effectively bound to the active sites of EGFR, MMP-9, and TSP-1, which led to reduced EGFR and MMP-9 protein expression ( p < 0.05 ), and increased TSP-1 ( P < 0.05 ), thereby inhibiting angiogenesis. These findings suggest that SBSG is a potential candidate for the nutraceuticals industry for angiogenesis management. • SBSG significantly suppressed the tube formation in the HUVECs while decreasing vascular density in CAM. • SBSG significantly lowered the protein levels of MMP-9 and EGFR, while increasing the protein levels of TSP-1. • SBSG hindered angiogenesis in the bladder cancer pathway. • SBSG is a potential candidate for the nutraceuticals industry for angiogenesis management.