A study to determine the apoptotic effects of gold (I) n-heterocyclic carbene compounds on fret-based breast cancer cells
Mubaraka D/O Yusuf
Date of Issue2016-05-26
School of Chemical and Biomedical Engineering
Breast cancer is the most common cancer in women worldwide. The chemotherapy currently available have some harmful side effects. Hence, novel drug discovery is very significant. NHC compounds are established as anti-mitochondrial agents that target tumorigenic mitochondria selectively and cause cell death. Current methods to investigate the cell viability are invasive and not sensitive. However, FRET is non-invasive and gives real-time analysis of apoptosis in breast cancer cells. In this study, apoptotic effects of Gold (I) NHC compounds on MDA-MB-231 breast cancer cells transfected with C3 biosensor was examined. Possible anti-cancer drug hits from the pool of compounds was also determined. All the 17 compounds and the drugs were incubated with the breast cancer cells. FRET images of all the drugs and compounds were taken from Day 1 to Day 3. Furthermore, cell viability and cell growth inhibition rate was quantified using MTT assay. Results show that with the conjugation of bromine to Gold (I) NHC compounds, cell viability decrease tremendously. FRET images clearly correlate with cell viability results suggesting the sensitivity of FRET technology. The effectiveness of the NHC compounds is supplementary proven by confocal imaging. 10 compounds out of the 17 compounds were narrowed down as a potential anti-tumor drug hits. In future, additional experiments on this 10 compounds such as animal studies, mitochondrial membrane potential assay, incubating the compounds with 3D cell culture, investigating the compounds in co-cultures of breast cancer cells and endothelial cells can be conducted to completely assess their anti-cancer effect.
Final Year Project (FYP)
Nanyang Technological University