SUSANTO, ANITA CAROLINE (2023) SYNERGY EFFECT OF α-PHELLANDRENE AND 5-FLUOROURACIL ON ANTI-PROLIFERATION IN COLORECTAL CANCER CELLS. Masters thesis, Universitas Katholik Soegijapranata Semarang.
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Abstract
Alpha-phellandrene (α-PA), an important component of dill, has been shown to have many physiological effects, including chemoprevention. However, the synergy effect of α-PA with chemotherapy medicines is limited. Colorectal cancer (CRC) ranked second as the most common cause of death globally, and it has a high incidence rate in Taiwan and Indonesia. One of the most frequently used medicines for chemotherapy for colorectal cancer is 5-fluorouracil (5-FU). Unfortunately, high doses and long-term use of 5-FU can generate side effects, such as those toxicity and inflammation, for CRC patients. This study investigates the synergy effect of α-PA combined with 5-FU on anti-proliferation in human colorectal HT-29 cancer cells. This study analyzed cell viability, cell proliferation, cell cycle and its regulators, apoptosis and its regulators, and cell death via the NF-ĸB pathway towards HT-29 after 50, 100, or 250 μM α-PA combined 5 μM 5-FU treatment for 72 h. Our results show that combining 250 μM α-PA and 5-FU treatment can reduce cell viability and fluorodeoxyuridine (FdU) incorporation level more than the 5-FU alone group (p<0.05). Reducing FdU levels means the combination of α-PA and 5-FU has a synergy effect inhibiting cell proliferation. Cell proliferation is also inhibited by 250 μM α-PA combined 5-FU due to cell cycle arrest in the G1 phase (p<0.05). As compared to the 5-FU treatment alone group, the combination treatment of 100 and 250 μM α-PA and 5-FU can more efficiently activate p21, 50 and 100 μM α-PA combined 5-FU can significantly decrease CDK2 levels (p<0.05), and 250 μM α-PA combined 5-FU can significantly reduce CDK-4 levels (p<0.05) in HT-29 cells. Combination of 50, 100, and 250 μM α-PA and 5-FU significantly reduce Wnt and p-β-catenin expression level, induce β-catenin translocation, and significantly reduce Wnt/β-catenin ratio (p<0.05) in HT-29 cells. Besides, this combination treatment of 50, 100, and 250 μM α-PA and 5-FU can more efficiently induce both early (by Annexin V stained) and late (by PI stained) apoptosis by reducing the mitochondria membrane potential (MMP), increasing Bax, Cytochrome C, Caspase-8, Bid, Caspase-9, and Caspase-3, also reducing Bcl-2 than the 5-FU treatment alone (p<0.05). The combination treatment of 50, 100, and 250 μM α-PA and 5-FU also more efficiently activates the NF-ĸB pathway by inducing p-IĸB, NF-ĸB (p65) translocation, and NF-ĸB DNA binding. NF-ĸB pathway activation resulted in the translocation of NF-ĸB in the mitochondria, reducing the VIII binding of HK-2 and VDAC-1 complexes and leading to apoptosis. These results show that α-PA is a safe phytochemical that is not toxic to human cells and has efficiency and high potential as a synergic chemotherapy component of 5-FU. These synergic effects reduce cell proliferation, induce apoptosis via intrinsic and extrinsic apoptotic pathways, and activate the NF-κB signaling pathway.
| Item Type: | Thesis (Masters) |
|---|---|
| Subjects: | 600 Technology (Applied sciences) > 660 Chemical engineering > 664 Food technology |
| Divisions: | Graduate Program in Master of Food Technology |
| Depositing User: | mr AM. Pudja Adjie Sudoso |
| Date Deposited: | 02 Oct 2023 07:08 |
| Last Modified: | 02 Oct 2023 07:08 |
| URI: | http://repository.unika.ac.id/id/eprint/33028 |
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