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Doctoral Degrees (Physiology)

Permanent URI for this collectionhttps://hdl.handle.net/10413/7045

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Browsing Doctoral Degrees (Physiology) by Subject "Breast Cancer."

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    The effect of isolated and nanoencapsulated flavonoids from Eriocephalus africanus on apoptotic factors and microRNA expression in cancer.
    (2020) Magura, Judie.; Mackraj, Irene.; Moodley, Roshila.
    Cancer continues to be a major health burden worldwide, with millions of new cases being diagnosed each year. Among women breast cancer remains a leading cause of cancer-related morbidity and mortality globally, despite the significant advances in detection and individualised treatments. The ideal non-surgical approach for the treatment of breast cancer would be anticancer therapeutics that are delivered directly to the tumour site for complete elimination of cancerous cells without being toxic to surrounding healthy cells. However, current chemotherapeutics encounter numerous challenges due to adverse side effects and progressive drug resistance albeit effective. In light of this, identifying new effective therapies with minimal toxic and chemosensitizing effects as well as target specificity is crucial in combating cancer. Emerging evidence has supported the use of plant-derived chemicals as novel alternative treatment options, owing to their minimal side effects and toxicity. Plant-derived polyphenols have gained considerable research interest due to their ability to inhibit proliferation, initiate apoptosis and arrest the cell cycle of cancerous cells by modulating related pathways. Furthermore, incorporation of active plant-derived polyphenols into novel technologies such as nanosystems, offers more optimal therapies through improved bioavailability and target specificity. In this regard, this study demonstrates, for the first time, the potential of phytochemicals isolated from the methanolic extract of the medicinal plant, Eriocephalus africanus, as an alternative therapeutic strategy in breast cancer treatment using ER-positive human adenocarcinoma (MCF-7) cell lines. Spectroscopic techniques including nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and mass spectrometry (MS) were used to identify the isolated compounds as hesperidin (flavanone), luteolin (flavone) and apigenin (flavone). Preliminary anticancer screening using the 3-(4,5dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay revealed hesperidin and luteolin to be potent against MCF-7. Dysregulated cellular apoptotic death is a hallmark of cancer and chemotherapy resistance; thus, the development of anticancer drugs targeting apoptosis is a widely used, effective anticancer treatment strategy. In this study, the efficacy of hesperidin and luteolin in targeting the apoptotic pathway was evaluated. Treatment of breast cancer cells with hesperidin and luteolin resulted in the downregulated expression of key anti-apoptotic Bcl-2; upregulated expression of pro-apoptotic Bax and caspases -8, -9 and -3. In addition, hesperidin and luteolin demonstrated the ability to effect epigenetic control through altering the expression of apoptotic microRNAs (-16, -21 and -34a). Moreover, treatment with hesperidin and luteolin resulted in significant accumulation of MCF-7 apoptotic cells into the G0/G1 and sub-G1 cell cycle phases, respectively. Encapsulation of hesperidin into nanoemulsions improved the cytotoxic and apoptotic effects in MCF-7 without being cytotoxic to non-cancerous human cell lines (HEK 293), halted the progression of the MCF-7 cells in the G2/M phase, and exhibited potential therapeutic activity through inhibiting the expression of oncomirs miR-21 and -155 overexpressed in breast cancer. Encapsulation of luteolin into solid nanoparticles generated from cleaved stearylamine exhibited non-selective cytotoxicity and decreased cell viability (< 10%) in both MCF-7 and HEK 293 cells, thus no further investigations were conducted using luteolin-loaded solid nanoparticles. Collectively, findings from this study provide new evidence on the effects of flavonoids isolated from E. africanus on apoptotic and epigenetic control in breast cancer, increasing our knowledge of the molecular basis of their anticancer activity.