Investigating the potential of acetyl plumbagin to reduce cancer-related drug resistance in various breast cancer cell lines
| dc.contributor.author | Palma, Gabriella Bianca Henriques | |
| dc.date.accessioned | 2019-05-20T06:34:06Z | |
| dc.date.available | 2019-05-20T06:34:06Z | |
| dc.date.issued | 2019 | |
| dc.description | A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science 2019 | en_ZA |
| dc.description.abstract | Breast cancer (BC) is the second most common malignancy comprising of 21.78% of all cancers in women. Death rates have decreased significantly from BC due to improved use of adjuvant Tamoxifen (Tam) and chemotherapy. However, given the improvement of survival rates due to endocrine therapies, many patients relapse with acquired resistance at later times after initial response. Thus a greater understanding of the mechanisms involved in cancerrelated drug resistance is needed along with the identification of new compounds that could help overcome drug resistance in cancer cells. The aim of this investigation was to test Acetyl Plumbagin (AP) as an adjuvant compound in various estrogen receptor positive (ER+) BC cell lines to reduce cholesterol accumulation and cancer-related resistance. This study observed the changes in pathways affected in two BC cell lines when AP was added alone and when AP was added in combination with Tam. This allowed for the observation of enhanced efficacy of Tam in inhibiting cell growth in MCF7 and long-term estrogen deprived (LTED) cells by 500% and 300% respectively. A significant increase in early-stage apoptosis was observed when cells were treated with the combination therapy as compared to single treatments. Cholesterol depletion was observed in both cell lines indicating that Tam and AP work in a synergistic manner in inducing apoptosis via cholesterol depletion in cell membranes. AP significantly enhanced the sensitivity of ER+ BC cells to Tam treatment. This indicates that AP could act as an anti-cancer lead compound for future drug development, targeting cholesterol accumulation and Tam resistance in BC. | en_ZA |
| dc.description.librarian | XL2019 | en_ZA |
| dc.identifier.uri | https://hdl.handle.net/10539/27056 | |
| dc.language.iso | en | en_ZA |
| dc.title | Investigating the potential of acetyl plumbagin to reduce cancer-related drug resistance in various breast cancer cell lines | en_ZA |
| dc.type | Thesis | en_ZA |
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