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dc.contributor.advisorYang, Jianen_US
dc.creatorAbuhussein, Omaren_US
dc.date.accessioned2016-02-09T12:00:14Z
dc.date.available2016-02-09T12:00:14Z
dc.date.created2016-01en_US
dc.date.issued2016-02-08en_US
dc.date.submittedJanuary 2016en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2016-01-2406en_US
dc.description.abstractBreast cancer is one of the most common malignancy diagnosed in women and is the primary cause of cancer-related deaths in women worldwide. It is a heterogeneous group of diseases that have a different response, prognosis, and clinical outcomes. Estrogen, progesterone and HER2 negative breast cancer, known as triple negative breast cancer (TNBC), does not respond to hormonal therapy. Basal-like breast cancer (BLBC) has shorter overall survival rate among other subtypes. Tumors sharing both TNBC and BLBC are considered less responsive to currently available treatment. Chemoresistance to treatment has been a challenge in cancer biology and force investigation toward developing new targeted therapies, which selectively target specific subtypes. Sphingolipid metabolites have an important physiological role in determining cell fate. Sphingolipid metabolites, ceramide, sphingosine, and sphingosine-1-phosphate (S1P), are implicated in cancer. S1P exerts its functions via extracellular and intracellular targets. S1P synthesized inside the cell is exported outside and binds to G-protein coupled receptors, the sphingosine-1-phosphate receptors 1-5 (S1PR1-5). Although the intracellular function is not well defined, its suggested intracellular S1P promotes cell apoptosis. The S1P pathway has received great attention recently due its function in cell survival and death. This effect was reported to be concentration dependent. In this research, I focused on S1P effect on nine TNBC/BLBC cell lines. I examined the in-vitro effects of S1P on apoptosis, proliferation, and cytotoxicity in triple negative/ basal-like breast cancer cell lines. Moreover, I studied the co-administration of S1P with currently used chemotherapeutic agents in these cell lines. Data show that S1P can selectively induce cell death in TNBC/BLBC cell lines at a specific concentration. In this research, I found that the mechanism of cell death following treatment with different S1P concentrations was mainly due to apoptosis. Results show that S1P leads to cell shrinkage, rounding and detachment in the nine TNBC/BLBC cell lines. S1P combination with doxorubicin and docetaxel at different concentrations shows no beneficial effect of the combination compared to the chemotherapeuitc agent alone. In some cell lines, the combination showed a protective effect. Further studies are required to determine the mechanism by which S1P induces cell apoptosis, inhibits cell growth, and demonstrates lack of responsiveness in combination studies.en_US
dc.language.isoengen_US
dc.subjectSphingosine-1-Phosphateen_US
dc.subjectTriple negative breast canceren_US
dc.subjectBasal-like breast cancer Cytotoxicityen_US
dc.subjectApoptosisen_US
dc.subjectProliferationen_US
dc.subjectChemotherapyen_US
dc.titleCytotoxic Activity of Sphingosine-1-Phosphate against Human Triple-negative/ Basal-like Breast Canceren_US
thesis.degree.departmentPharmacy and Nutritionen_US
thesis.degree.disciplinePharmacyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberAlcorn, Janeen_US
dc.contributor.committeeMemberVizeacoumar, Francoen_US
dc.contributor.committeeMemberCayabyab, Franciscoen_US


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