School of Environment and Life Sciences, Cockcroft Building, University of Salford, Manchester M5 4WT, UK.
Mar Drugs. 2018 Feb 15;16(2):63. doi: 10.3390/md16020063.
Despite the increasing availability of new classes of cancer treatment, such as immune- and targeted therapies, there remains a need for the development of new antiproliferative/cytotoxic drugs with improved pharmacological profiles that can also overcome drug resistant forms of cancer. In this study, we have identified, and characterised, a novel marine polysaccharide with the potential to be developed as an anticancer agent. Sulphated polysaccharides isolated from the common cockle () were shown to have antiproliferative activity on chronic myelogenous leukaemia and relapsed acute lymphoblastic leukaemia cell lines. Disaccharide and monosaccharide analysis of these marine polysaccharides confirmed the presence of glycosaminoglycan-like structures that were enriched in ion-exchange purified fractions containing antiproliferative activity. The antiproliferative activity of these glycosaminoglycan-like marine polysaccharides was shown to be susceptible to heparinase but not chondrotinase ABC digestion. This pattern of enzymatic and antiproliferative activity has not previously been seen, with either marine or mammalian glycosaminoglycans. As such, our findings suggest we have identified a new type of marine derived heparan sulphate/heparin-like polysaccharide with potent anticancer properties.
尽管越来越多的新型癌症治疗药物，如免疫治疗和靶向治疗药物，已经问世，但仍然需要开发具有改善的药理学特性的新型抗增殖/细胞毒性药物，以克服癌症的耐药形式。在这项研究中，我们已经鉴定并表征了一种具有开发为抗癌剂潜力的新型海洋多糖。从普通贻贝（）中分离出的硫酸多糖对慢性髓系白血病和复发性急性淋巴细胞白血病细胞系具有抗增殖活性。对这些海洋多糖的二糖和单糖分析证实了存在类似糖胺聚糖的结构，这些结构在富含具有抗增殖活性的离子交换纯化级分中富集。这些类似糖胺聚糖的海洋多糖的抗增殖活性易受肝素酶但不易受软骨素酶 ABC 消化的影响。这种酶促和抗增殖活性的模式以前在海洋或哺乳动物糖胺聚糖中都没有见过。因此，我们的研究结果表明，我们已经鉴定出一种具有潜在抗癌特性的新型海洋来源的硫酸乙酰肝素/肝素样多糖。
