Anti-Vasculogenic Activity of a Polysaccharide Derived from Brittle Star via Inhibition of VEGF, Paxillin and MMP-9

[摘要] Background: Bioactive compounds such as terpenoids, chondroitin sulfate, and polysaccharides with added value can be found in prestine marine creatures. These compounds often do have highly valuable therapeutic applications such as being antioxidant, antitumorogenic, anti-inflammatory and anti-angiogenic. For the latter, varieties of angiogenesis factors can suppress this issue within the bodily tissues. Objectives: The anti-angiogenic and anti-metastatic capacity of a polysaccharide derived from brittle star was investigated. Material and Methods: The anti-proliferative effect of derived polysaccharide on umbilical vein endothelial cells (HUVEC) was measured using MTT (dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. The anti-angiogenic effect of the isolated polysaccharide was examined by Chorioallantoic membrane (CAM) assay. The transcriptional expression of VEGF (Vascular Endothelial Growth Factor) was evaluated by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The anti-metastatic activity was investigated via scratch-wound healing assay. The levels of Paxillin and Matrix Metalloproteinase-9 (MMP-9) expression were analyzed by RT-PCR. Statistical analysis and mean comparisons (p< 0.05) were carried out by SPSS 16. Results: Our results elucidated that the brittle star isolated polysaccharide exerted a dose dependent cytotoxic effect on the HUVEC endothelial cells. The CAM assay exhibited potent anti-angiogenic activity in vivo. The RT-PCR analysis showed that the extracted polysaccharide (40, 60 µg.mL-1) down-regulated the VEGF expression. Further, the diminished attachment of endothelial cells demonstrated that the anti-invasiveness of the derived polysaccharide (25, 50 µg.mL-1) was administrated via down-regulation of paxillin and MMP-9 mRNA expression. Conclusions: Taken together, these results indicated that the polysaccharide extracted from brittle star was able to decrease the viability of the HUVEC cells, to suppress angiogenesis, and possibly act as a natural anti-angiogenic and anti-metastatic marine organic compound against angiogenesis related pathologies.

[学科分类] 生物技术

[关键词] Angiogenesis;Chick Chorioallantoic Membrane;Endothelial cells;MMP-9;VEGF