The effects of fucosylated chondroitin sulfate isolated from Isostichopus badionotus on antimetastatic activity via down-regulation of Hif-1α and Hpa

Fucosylated chondroitin sulfate (CHS) was prepared from the sea cucumber Isostichopus badionotus (Ib-CHS), and the antimetastatic effect was studied using cell adhesion, migration, invasion, chorioallntoic membrane (CAM), and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Ib-CHS remarkably suppressed proliferation of 95D cells, and inhibited adhesion, migration, and invasion of 95D cells in a dose-dependent manner. CAM assay results suggested that Ib-CHS attenuates neovascularization in the chick embryo. RT-PCR analyses revealed that Ib-CHS dramatically decreased expression of matrix metalloproteinase-2/9 (MMP-2/9), hypoxia-inducible factor (Hif-1 alpha), heparanase (Hpa), and vascular endothelial growth factor (VEGF), and increased expression levels of the tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), important inhibitors of MMP-2/9. Ib-CHS markedly inhibited tumor growth, improved the metastatic foci occurrence rate, and down-regulated expressions of Hif-1 alpha, Hpa, and VEGF in vivo. Ib-CHS exerted antimetastatic activities in vitro and in vivo.