title: Modulation of the binding of basic fibroblast growth factor and heparanase activity by purified λ-carrageenan oligosaccharides.
abstract: Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as promising agents for cancer therapy. Here, we report λ-carrageenan oligosaccharides (λ-COs), highly-sulfated oligosaccharides acting as a basic fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. λ-COs with degree of polymerization (DP) from 2 to 8 degraded by λ-carrageenase were separated and purified. The structures were identified by mass spectrometry. The activities of λ-COs are closely related with DP. λ-COs showed no cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, λ-carraheptaose showed highest capability. Only λ-carraheptaose can effectively bind to bFGF. Binding kinetics showed that λ-carraheptaose and suramin had different binding modes, i.e., suramin displayed a fast association and fast dissociation, but λ-carraheptaose exhibited a slow association and slow dissociation. In addition, λ-COs showed the highest heparanase inhibitory ability and abolished the endothelial cell invasion. Thus, λ-COs may provide a tool to develop of new carbohydrate-based therapeutics against cancer and angiogenesis.
authors: School of Marine Science, Ningbo University, Ningbo 315211, China. Electronic address: 657208616@qq.com.
authors: Ting-Ting
authors: TT
authors: Niu
authors: School of Marine Science, Ningbo University, Ningbo 315211, China. Electronic address: 362931093@qq.com.
authors: Dong-Sheng
authors: DS
authors: Zhang
authors: School of Marine Science, Ningbo University, Ningbo 315211, China. Electronic address: chenhaimin@nbu.edu.cn.
authors: Hai-Min
authors: HM
authors: Chen
authors: School of Marine Science, Ningbo University, Ningbo 315211, China. Electronic address: yanxiaojun@nbu.edu.cn.
authors: Xiao-Jun
authors: XJ
authors: Yan
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002351:Carrageenan / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000378:metabolism*; D005966:Glucuronidase / Q000737:chemistry / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D000099175:Heparanase
chemical_list: D001426:Bacterial Proteins; D002351:Carrageenan; D005346:Fibroblast Growth Factors; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D013498:Suramin; D000099175:Heparanase; C516835:lambda-carrageenase, Pseudoalteromonas
keywords: Basic fibroblast growth factor; Heparanase; Heparin sulfate mimic; λ-Carrageenan oligosaccharides