Anti-proliferative effects of selected terpenoids and programmed cell death susceptibility of betulin on the human breast cancer cell lines

• 主要作者: Robert, Alex Walzico
• 格式: Thesis
• 语言: 英语; 英语
• 出版: 2020
• 主题: QP501-801 Animal biochemistry
• 在线阅读: https://eprints.ums.edu.my/id/eprint/42603/1/24%20PAGES.pdf; https://eprints.ums.edu.my/id/eprint/42603/2/FULLTEXT.pdf

An increasing number of terpenoids that possess anticancer activity has attracted researchers' attention worldwide. This study focused on how selected terpenoids affect the cell proliferation, morphology alteration and the mechanism of cell death in breast cancer cells. The results in anti-proliferative assay showed that betulin and lupeol inhibited cell proliferation of MCF-7 with ICso 13.97±3.02 μg/ml and 24.67±1.15 μg/ml, respectively. Both compounds also inhibited MDA-MB-231 with the IC50 12.0 8±0.38 μg/ml for betulin and 17.0 0±1.09 μg/ml for lupeol. The anti-proliferation assay was also tested on normal embryonic kidney cells (293T) and the results suggested that betulin did not affect the cell proliferation in normal cell when compared to lupeol with ICso 17.17±1.04 μg/ml. Squalene did not exert any effect on all cells' proliferation. Betulin was then selected for further apoptosis and morphology investigation by DNA fragmentation, DAPI and scaning electron microscopy analysis. Betulin appeared to induce apoptosis with DNA laddering effects and apoptotic-related morphological changes when examined using DAPI and SEM. Betulin treatment on MCF-7 and MDA-MB-231 were then subjected gene expression analysis by RT-PCR with 9 genes related to apoptosis (BAX BCL,..2/ Caspase-3/ MYC and PTEN), autophagy (ATG-5 and BECN-1) and necrosis (CYLD-1 and RIPK-1). Further examination on the protein expression with apoptosis-related protein such as BAX, BCL-2, Caspase-3 and P53. Taken together, the results on gene and protein expression analysis showed that betulin demonstrated the capability in inducing cell death but not limited to apoptosis only as it might trigger other pathways that activated cell death such as autophagy and necrosis. In conclusion, further study must be conducted to understand more of the inter-relations between these cell deaths caused by betulin as this compound has the potential to be developed into a promising anticancer agent.