Isolation and characterisation of novel glycosaminoglycan-like polysaccharides derived from marine molluscs with antiproliferative activity

Aldairi, AF 2018, Isolation and characterisation of novel glycosaminoglycan-like polysaccharides derived from marine molluscs with antiproliferative activity , PhD thesis, University of Salford.

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Abstract

Although various anticancer therapeutic tools have been launched, such as immunotherapy and targeted therapy, newly developed drugs with antiproliferative/cytotoxic effects are still in demand; hence, newly discovered anticancer drugs with an improved pharmacological profile are needed to overcome drug resistance of cancer cells. This study focused on identifying and characterising novel polysaccharides isolated from the common cockle (Cerastoderma edule) with antiproliferative activity, using the cetylpyridinium chloride precipitation method. Marine polysaccharides have exhibited in-vitro potent antiproliferative activity, leading to induced apoptotic cellular death in three cancer cell lines, which are chronic myelogenous leukaemia, relapsed acute lymphoblastic leukaemia and mesothelioma of the pleural cavity with asbestos exposure. Structural analysis has confirmed the presence of glycosaminoglycan-like polysaccharides in cockle extracts with potent antiproliferative activity, which are susceptible to three classes of heparinase enzymes, which has not been seen previously, but not to chondroitinase enzymes. Cockle polysaccharide purification using anion-exchange chromatography has generated six peaks (1-6); however, only fraction 5 exhibited antiproliferative activity, which was determined to be susceptible to heparinase enzymes. Surprisingly, some sequence of resistance to heparinase was observed within cockle polysaccharide chains; therefore, a new type of marine-derived heparan sulphate/heparin-like polysaccharide with potent anticancer properties was suggested, as none of the mammalian glycosaminoglycans exhibited antiproliferative activity on cancer cell lines. Overall, the final structural characterisation did confirm the presence of fucosylated polysaccharide, N- and O-linked glycans, in addition to HS-like structures. These various chains made creating the final judgment about cockle polysaccharide structural elucidation very challenging because of sample complexity.

Item Type: Thesis (PhD)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Schools > School of Environment and Life Sciences
Funders: Umm Al-Qura University and the ministry of higher education of Saudi Arabia
Depositing User: Abdullah Aldairi
Date Deposited: 03 Jul 2019 12:53
Last Modified: 03 Jan 2020 02:30
URI: http://usir.salford.ac.uk/id/eprint/51353

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