Insight into the relationships of structure and anti-tumor effects of Glucuronomannan oligosaccharides (Gx) and its derivatives on the A549 lung adenocarcinoma cells

Lung cancer is a malignant disease that causes death worldwide. Glucuronomannan oligosaccharides (Gx) as a subtype of fucoidan -a broad-spectrum anti-tumor agent, were hypothesized to be effective on lung carcinoma. The effects of sulfate contents and degree of polymerization on Gx and its sulfated derivatives (GxSy) were discussed via MTT assay, migration and invasion assays, and western blotting assay in vitro. The anti-proliferation activities were directly related to the sulfate contents of sulfated G4 and G6 on A549 cells. Furthermore, GxSy suppressed cell metastasis more effectively than Gx. Further analysis indicated that sulfated G2 inhibited cell metastasis by down-regulating the FAK-PI3K-AKT-mTOR pathway, whereas sulfated G4 down-regulated VEGFR2-mediated FAK/MMPs pathway and up-regulated TSC2 protein. In addition, sulfated G6 activates the FAK-mTOR pathway. While in unsulfated Gx groups, there were no special rules for the FAK-mTOR pathway by varying degrees of polymerization. Taken together, the anti-tumor activity of GxSy was more correlated with sulfate contents than polymerization degree. These sparked the consideration of appropriate modification as a useful strategy for drug discovery.