期刊
CARBOHYDRATE POLYMERS
卷 125, 期 -, 页码 76-84出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2015.02.069
关键词
lambda-Carrageenan oligosaccharides; Basic fibroblast growth factor; Heparanase; Heparin sulfate mimic
资金
- NSFC project [81370532]
- National Spark Major Project [2013GA701001]
- Ningbo Marine Algae Biotechnology Team [2011881007]
- K.C. Wong Magna Fund in Ningbo University
- 151 Talents Project
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.
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