Modulation of the binding of basic fibroblast growth factor and heparanase activity by purified λ-carrageenan oligosaccharides

Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as promising agents for cancer therapy. Here, we report lambda-carrageenan oligosaccharides (lambda-COs), highly-sulfated oligosaccharides acting as a basic fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. lambda-COs with degree of polymerization (DP) from 2 to 8 degraded by lambda-carrageenase were separated and purified. The structures were identified by mass spectrometry. The activities of lambda-COs are closely related with DP. lambda-COs showed no cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, lambda-carraheptaose showed highest capability. Only lambda-carraheptaose can effectively bind to bFGF. Binding kinetics showed that lambda-carraheptaose and suramin had different binding modes, i.e., suramin displayed a fast association and fast dissociation, but lambda-carraheptaose exhibited a slow association and slow dissociation. In addition, lambda-COs showed the highest heparanase inhibitory ability and abolished the endothelial cell invasion. Thus, lambda-COs may provide a tool to develop of new carbohydrate-based therapeutics against cancer and angiogenesis. (C) 2015 Elsevier Ltd. All rights reserved.