Apoptosis and cell cycle mechanisms of ampelopsin E on triple negative breast cancer cells
Cancer remains as the second leading cause of death after cardiovascular disease, worldwide. Approximately 14.1 million new cancer cases and 8.2 million cancer deaths were reported in 2012. Breast cancer is the most common cancer among women with 522,000 deaths in 2012 alone. There are a few t...
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| Format: | Thesis |
| Language: | English |
| Published: |
2017
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| Online Access: | http://psasir.upm.edu.my/id/eprint/69193/1/IB%202018%206%20IR.pdf http://psasir.upm.edu.my/id/eprint/69193/ |
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| Summary: | Cancer remains as the second leading cause of death after cardiovascular disease,
worldwide. Approximately 14.1 million new cancer cases and 8.2 million cancer
deaths were reported in 2012. Breast cancer is the most common cancer among
women with 522,000 deaths in 2012 alone. There are a few treatment modalities for
breast cancer that include chemotherapy, mastectomy, biological therapy and hormone
replacement therapy. Chemotherapy remains as the main treatment, but it comes with
severe side effects such as immunosuppression and formation of secondary tumor.
Therefore, people now are turning to natural products that include the use of plant as
an alternative for management of the cancer. Indeed, plants have been a good source of
a few anticancer drugs such as taxol, vincristine and vinblastine. Dryobalanops or also
known as Kapur can be found in tropical rain forest of West Malesia (Peninsular
Malaysia, Borneo and Sumatra). There are only seven species of Dryobalanops, which
are D. rappa, D. aromatica, D. lanceolata, D. beccari, D. fusca, D. keithii and D.
oblongifolia. Resveratrol oligomer is a major group of bioactive compounds that can
be found in Dryobalanops species was reported to exhibit antioxidant, antifungal,
anti-HIV, anti-platelet aggregation, tyrosinase and cyclooxygenase I and II inhibitory
properties. The objective of this study was to determine the cytotoxicity of resveratrol
oligomers (ampelopsin E, ampelopsin F, flexuosol A, laevifonol, Malaysianol A,
Malaysianol D and nepalensinol E) from Dryobalanops species towards non-hormone
dependent (MDA-MB-231) and hormone dependent (MCF-7) breast cancer, human
colorectal adenocarcinoma cancer (HT-29), alveolar carcinoma (A-549), cervical
adenocarcinoma (HeLa), non-tumorigenic epithelial breast (MCF-10A) and mouse
embryonic fibroblast (NIH/3T3) cells. The cytotoxicity was determined by MTT assay.
The cells were treated with the compounds (0.94-30 μM) for 72 hours. The mode of
cell death was evaluated by using an inverted light microscope and annexin V/PI
flow-cytometry analysis. Cell cycle analysis was performed by using a flow cytometer.
Effects of ampelopsin E on the expression of NF-κB, p53, p21, Cyclin A, Cyclin B1,
CDK1, Bax and Bcl-2 were analysed by using Western blotting. Data showed that
ampelopsin E was most cytotoxic towards MDA-MB-231 cells with the IC50 (50%
inhibition of cell viability compared to the control) of 14.5±0.71 μM. Cell shrinkage,
membrane blebbing and formation apoptotic bodies characteristic of apoptosis were observed following treatment with ampelopsin E. The annexin V/PI flow cytometric
analysis further confirmed that ampelopsin E induced apoptosis in MDA-MB-231
cells. Cell cycle analysis revealed that ampelopsin E induced G2/M phase cell cycle
arrest in the cells. The expression level of Bax and p21 was significantly up-regulated
(p<0.05), whereas, the expression level of NF-κB, p53, Cyclin A, Cyclin B1, CDK1
and Bcl-2 was significantly down-regulated (p<0.05) after treatment with ampelopsin
E. In conclusion, ampelopsin E induced apoptosis and cell cycle arrest in
MDA-MB-231 cells. It is postulated that the induction of apoptosis is via NF-κB
p53/p21 and intrinsic pathways, and the G2/M arrest is via p53-independent/p21
pathway. Therefore, ampelopsin E has the potential to be developed into an anticancer
agent for the treatment of triple negative breast cancer. |
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