3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Screening of South African medicinal plant Euphorbia tirucalli for anticancer properties(2015) Choene, Mpho SusanCancer is an enormous burden of disease, accounting for millions of deaths annually worldwide. Today, more people are dying from cancer than HIV/AIDS, malaria and tuberculosis combined. According to the American Cancer Society, it is expected that the global cancer burden will double by 2030 if preventative measures are not applied. Breast and gynaecological cancers remains a big scourge in developing countries, with breast cancer being the most common cancer and gynaecological cancers accounting for approximately 25% of all cancers in women in developing countries. Currently, the standard cancer treatments include surgery, radiation and chemotherapy. Adverse toxicities have been associated with these therapies and their effectiveness is also limited to drug resistance. The cost of treatment is another major burden. Limitations associated with these conventional cancer treatments have made discoveries of novel therapeutics which exhibit less toxicity and at a lowered cost of paramount importance. Medicinal plant extracts have recently attracted attention to modern medical science research with their non-lethal activity. Currently, up to 50% of the world drugs including chemotherapeutic drugs such as taxol and camptothecin are made from natural products or their derivatives. In this study we aimed to investigate the anti-cancer properties of the medicinal plant Euphorbia tirucalli. The crude extracts of E. tirucalli extracted using butanol; hexane and methanol solvents were screened for antiproliferative activity in breast (MCF-7 and MDA-MB231), ovarian (RMG-1) and cervical (SiHa) cancer cell lines. MTT assay and Real-Time Cell Analyzer (RTCA), xCELLigence were used to determine cytotoxicity of the extracts and calculate IC50. From MTT and xCELLigence results, we observed that E. tirucalli extracts exhibited dose-dependent inhibition of cell proliferation with RMG-1 and MCF-7 cells being more sensitive than MDA-MB231 and SiHa cells to all three extracts for an unclear reason. The butanol extract appeared to exhibit iv the most cytotoxicity with all cell lines reaching IC50 at low extract concentrations. Most therapies in anticancer treatment, such as chemotherapy, mainly induce cell death by causing either G0/G1 or G2/M cell cycle arrest and then inducing an apoptotic pathway. Therefore, cell cycle arrest and the induction of apoptosis in cancer cells become the major indicators of anticancer effects. Cells were stained with propidium iodide dye to determine if cells were arrested at G0/G1 or G2/M cell cycle stages while annexin V and PI staining were used to determine the type of cell death induced by the extracts. Cell cycle analyses revealed MCF-7, MDA-MB231 and SiHa cancer cells underwent arrest at G0/G1 following treatment with the plant extracts. Annexin V and PI staining revealed different proportions of apoptotic and necrotic populations. The extracts mainly induced apoptosis on MCF-7 and MDA-MB 231 cells, with the butanolic extracts inducing the most apoptosis. RMG-1 and SiHa cells had a high proportion of cells undergoing both late apoptosis and necrosis. The molecular mechanism of cell death induction was investigated using real time PCR and western blot. From the gene expression studies, p21 was observed to be over expressed in all cells following all treatments, in line with the observed cell cycle arrest at G0/G1. The extrinsic pathway of apoptosis was identified as the type of cell death induced with caspase 8 being overexpressed in MDA-MB 231 cells treated with butanol and hexane extracts. Upon further fractionation, flavonoids and especially isorhamnetin were identified as the active compounds in these extracts. Overall, the plant contains compounds that have some activity against cell proliferation and can be a promising tool to treat cancer cells. However, more work needs to be done to verify which compounds are mainly involved.Item Evaluating the effect of South African Herbal extracts on breast cancer cells(2013-02-01) Choene, Mpho SusanIn this research we aimed to investigate the anti-proliferative properties of three South African plants: Kedrostis foetidissima, Euphorbia mauritanica and Elytropappus rhinocerotis against breast cancer cells. This was done on the basis of their documented ethno-medicinal use against cancer and other ailments. The plant extracts were screened for cytotoxicity and pro-apoptotic activity against two breast cancer cell lines MCF-7 and YMB-1. With an IC50 ~ 100 μg/ml, K. foetidissima was the only extract that exhibited significant cytotoxicity on both cell lines, whilst E. mauritanica was cytotoxic to MCF-7 cells only. The cytotoxicity assay was followed by the Annexin-V detection assay to evaluate the occurrence of apoptosis. The results observed suggested that K. foetidissima was inducing significant apoptosis on both YMB-1 and MCF-7 cells, whilst E. mauritanica was inducing significant apoptosis on MCF-7 cells. Since both K. foetidissima and E. mauritanica crude extracts induced apoptosis to MCF-7 cells, they were selected for gene expression studies on MCF-7 using real-time PCR. This was done with the aim of investigating if these extracts were having an effect on the tumour suppressors p53 and RBBP6, which were shown in previous studies to be deregulated in up to 50% of cancers. From the real-time PCR data we observed no changes in the expression levels of these genes following treatment with the herbal extracts. This may suggest that these plants have an effect on other components of the apoptotic pathway other than the tumour suppressors p53 and RBBP6. The antiproliferative activity observed whilst treating these particular cell lines with K. foetidissima and E. mauritanica suggests that these South African herbal plants present themselves as potential future cancer therapeutic agents; however, further studies on these herbal plants need to be performed to validate these results. KEYWORDS: Apoptosis Breast cancer Euphorbia mauritanica Kedrostis foetidissima p53