Chitooligosaccharides inhibit nitric oxide mediated migration of endothelial cells in vitro and tumor angiogenesis in vivo

Chitooligosaccharides (COS), with a polymerization degree of 2–8, were prepared by the enzymic hydrolysis of chitosan. The anti-angiogenic activity of COS in subcutaneous xenografts in mice has been studied for the first time. As nitric oxide (NO) plays a critical role in angiogenesis, we investigated the relationship between COS and the NO-mediated migration of endothelial cells. The results demonstrated that COS could suppress tumor angiogenesis and exhibit antioxidant activity by increasing the SOD activity in Kunming mice that were implanted with human breast cancer cells, dose-dependently. COS was able to inhibit the migration of endothelial cells induced by NO. In addition, COS altered the polymerization of actin and antagonized the formation of membrane extensions that were triggered by NO in endothelial cells. Together, these results indicated that COS had anti-angiogenic activity in vivo and in vitro, and the inhibitory activity of COS on endothelial cell migration may be due to interference with the NO signal transduction pathway.