Isolation and characterization of a glycosaminoglycan with anticancer activity

Ogundipe, OD 2015, Isolation and characterization of a glycosaminoglycan with anticancer activity , PhD thesis, University of Salford.

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Glycosaminoglycans (GAGs) are a family of complex mixture of linear polysaccharides that are present in both vertebrates and invertebrates. This polysaccharide plays important roles in physiological and pathological conditions, including cancer. In this study, GAGs were isolated from two different fish (whelks and cockles) belonging to mollusc invertebrates. The crude GAGs isolated from each shellfish demonstrated variable selective anti-cancer activities against many cancer cell lines including breast (MDANQ01 and MDA468), leukemia (MOLT-4 and K562) and ovarian (HeLa) cancer. None of the commercial GAGs exhibited any anti-cancer activities against all the cancer cells studied. Previous studies conducted on the isolation of GAGs from molluscs reported mainly its anti-coagulant and anti-inflammatory activities; thus neglecting its record of anti-cancer activity. All purified whelk fractions (A – D & F) obtained failed to show any anti-cancer activity; with the exception of fraction E, which showed equal levels of selective anti-cancer activity against breast cancer cells. Mechanism of cell death caused by the three novel GAGs on cancers cells were investigated via cell cycle analysis and apoptosis detection assay. Cell cycle analysis revealed significant perturbations in the cancer cell cycle showing cell cycle arrests at different stages. Similarly, there were significant apoptosis inductions induced by the three novel GAGs on each of the cell lines investigated. Structural elucidations of the two fish GAGs, using chemical, enzymatic, Polyacrylamide, Superose 12 size exclusion chromatography , gel filtration and SAX-HPLC methods of analysis, revealed the presence of both chondroitin sulfate (CS)/dermatan sulfate (DS)-like and HS-like GAGs. Discrepancies in the structural elucidations of the novel GAG mixtures and the commercial GAGs may be partly responsible for the anti-cancer activity of the novel polysaccharides, as changes in exogenous GAGs structural composition, especially sulfation levels or patterns, can alter its binding to growth factors, which is essential for cell proliferation.

Item Type: Thesis (PhD)
Themes: Built and Human Environment
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Schools > School of Environment and Life Sciences
Funders: Self funded
Depositing User: OD Ogundipe
Date Deposited: 26 Jul 2015 09:47
Last Modified: 27 Aug 2021 20:16

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