Comparative study on the mechanisms of anti-lung cancer activities of three sulfated galactofucans.

Abstract: Sulfated galactofucans, as the active compositions of fucoidan, were reported to exhibit anti-tumor activity. In the current study, a sulfated galactofucan (SGF) from Sargassum thunbergii and its three derivatives (SGF-H, SGF-L and SGF-S) were prepared for structural and anti-lung cancer activities analysis. Structural analysis showed that SGF-H was a high molecular weight sulfated galactofucan with a high molar ratio of galactose (Gal) to fucose (Fuc) (0.66:1), SGF-L was a low molecular weight sulfated galactofucan with a low molar ratio of Gal to Fuc (0.20:1) and SGF-S was a mixture of sulfated galacto-fuco-oligomers or fuco-oligomers. It is noteworthy that the linkage of Gal residues in SGF-H was a β-linkage while SGF-L was an α-linkage. A comparative study on the anti-lung cancer activity in vitro and in vivo, anti-metastatic effects, the metastasis-associated protein expression and binding abilities to fibroblast growth factors (FGFs) of SGF, SGF-H and SGF-L were performed to understand the structure-activity relationship. SGF-L showed the strongest activity in the inhibition of human lung cancer cells A549 cell proliferation while SGF-H exhibited the strongest activity in the inhibition of human bronchial epithelial cells BEAS-2B cell proliferation. SGF-L showed the strongest anti-metastatic activity, followed by SGF-H and SGF. The expression of metastasis-associated proteins showed only a small difference. The in vivo tumor inhibition of SGF, SGF-H and SGF-L were 45, 41 and 31%, respectively. SPR analysis showed SGF-H binding preferentially to FGF1 and FGF2 while SGF-L preferentially binds to FGF7 and FGF10, suggesting that the anti-lung cancer activity from sulfated galactofucan could involve the FGF-FAK/mTOR pathway.