Structure-activity relationship of propylene glycol alginate sodium sulfate derivatives for blockade of selectins binding to tumor cells. (15th April 2019) - Ma, He
Highlights: PSS effectively inhibited the binding of P- or L-selectin with LS180 and HL-60 cancer cells. The content of sulfate was crucial for the inhibitory effect of PSS. PSS with higher molecular weight exerted stronger inhibitory effect. Poly guluronic acid -chains possessed a preferential conformation for P-/L-selectin binding. PGGS significantly suppressed lung metastatic colonization in vivo . Abstract: Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effectively prevented the binding of P- or L-selectin with tumor cells. Moreover, the structure-activity relationship study indicated that the activity of PSS is related to the sulfate group at the C-2/C-3 position, the propylene glycol substituent at the C-6 position, the ratio of guluronic acid to mannuronic acid, and the molecular weight. Additionally, PSS derivatives significantly suppressed lung metastasis in vivo. Our results demonstrated that PSS and its derivatives are potential antimetastatic drugs candidates.