ETDs: Doctoral Theses

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Browsing ETDs: Doctoral Theses by Subject "4T1 breast cancer cells"

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    Uncovering the therapeutic potential of Uncaria tomentosa using B16-BL6 mouse melanoma and 4T1 mouse breast cancer cells
    (2019-03-14) Zari, Ali
    Uncaria tomentosa (Rubiaceae), a medicinal plant native to Peru, has been traditionally used for centuries as a treatment for a wide variety of diseases, as well as to maintain health. It grows primarily in the Amazon rainforest and throughout South and Central America. U. tomentosa extracts have been demonstrated to have anti-oxidant, anti-apoptotic, anti-inflammatory and anti-cancer properties. The goal of this study was to examine Uncaria tomentosa in both in vitro and in vivo models in order to evaluate its potential anti-cancer activity using the B16-BL6 mouse melanoma and 4T1 mouse breast cancer cell lines. Both ethanol and PBS extracts of U. tomentosa were prepared and used to measure the effects on cell growth and survival using several different methodologies. Treatment of cells with ethanol extracts was much more effective at inhibiting cancer cell growth than treatment with PBS extracts in vitro, but no significant differences in the cancer inhibitory effects were observed in vivo. The in vitro experiments showed that treatment with the U. tomentosa extract significantly inhibited the growth of both B16- BL6 and 4T1 cell lines. It also inhibited the expression of the Ki-67 proliferation marker and promoted cell death as measured by increased DNA fragmentation using TUNEL assays in cancer cells. Treatment with the ethanol extract of U. tomentosa caused a significant increase in the fraction of apoptotic cells in flow cytometry (i.e. sub G1 peaks). Furthermore, two animal experiments were performed in order to evaluate the effect of U. tomentosa treatment on B16-BL6 cells in C57BL/6 mice. The results of the in vivo experiments concluded that treatment with U. tomentosa reduced tumour weight and tumour size. Histochemical analysis of the B16-BL6 tumours showed a strong reduction in the Ki-67 cell proliferation marker and a small but not significant increase in DNA fragmentation in U. tomentosa-treated mice compared to the control. Further, U. tomentosa extracts reduced staining for Factor VIII, a marker for endothelial cells, indicating a decrease in angiogenesis in treated mice. Since U. tomentosa has been shown to affect immune system function, the infiltration of several different immune cells into the tumour was examined. No significant differences in the number of infiltrating T cells (including T helper and cytotoxic T cells), B cells, or platelets were found between the treated groups and the control. Collectively, the results in this study concluded that U. tomentosa has potent anticancer activity that significantly inhibited cancer cell growth both in vitro and in vivo. The discovery of new medicinal plants that are effective against cancer cells may provide a strategy to develop cancer therapy and requires more attention.