Role of epigallocatechin-3-gallate from green tea in iron chelation and endoplasmic reticulum stress pathway in colorectal cancer cells
CRC is ranked at the third place in the list of most common malignant disease in the world. However, common treatments like radiotherapy and chemotherapy will cause physical side effects to the patients such as hair loss, nausea, burnt effects on skin, loss of appetite and many others. Based o...
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/85552/1/FPSK%28M%29%202019%2052%20ir.pdf |
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| Summary: | CRC is ranked at the third place in the list of most common malignant disease in the
world. However, common treatments like radiotherapy and chemotherapy will cause
physical side effects to the patients such as hair loss, nausea, burnt effects on skin, loss
of appetite and many others. Based on the major scientific findings, epigallocatechin-
3-gallate (EGCG) is the most bioactive compound in green tea that is responsible for
all its health benefits. Hence, this study intends to find out the roles of EGCG when
targeting iron chelation and endoplasmic reticulum (ER) stress pathway in CRC. MTT
assay was first performed involving colorectal cancer cell line (HT-29) and normal
cell line which was embryonic fibroblast (3T3). Protein extraction and Western blot
were done to observe the related proteins expression. Caspase 3/7 assay was also
performed to determine apoptosis process induced by EGCG treatment.
Desferrioxamine (DFO) has been used as a positive control throughout the experiment.
From the MTT assay results, EGCG showed toxicity towards HT-29 at all
incubationtimes. The IC50 values obtained were 262.5 μM, 190.3 μM and 88.1 μM at
24h, 48h and 72h incubation times respectively. However, EGCG was not toxic on
3T3. EGCG had up-regulated transferrin (TfR) (p < 0.01) protein and down-regulated
ferritin-H (FtH) (p < 0.001) protein indicating that iron chelation activity has occurred
in HT-29. EGCG also had induced ER stress in HT-29 by up-regulating proteins like
immunoglobulin-binding (BiP) (p < 0.001), (PKR)-like endoplasmic reticulum kinase
(PERK) (p < 0.01), eukaryotic initiation factor 2 alpha subunit (eIF2α) (p < 0.001), peIF2α
(p < 0.01), activating transcription 4 (ATF4) (p < 0.01) and inositol requiring
kinase 1 alpha (IRE1α) (p < 0.01). However, EGCG did not affect activating
transcription factor 6 protein (ATF6) (p > 0.05). Due to iron chelation activity by
EGCG, this has caused iron depletion and generation of reactive oxygen species
(ROS) in the HT-29 cells. Subsequently, ER stress will be induced due to these causes and unfolded protein response (UPR) will be activated, resulting in apoptosis to occur.
In conclusion, EGCG is a potential compound to treat CRC by targeting iron chelation
and ER stress pathway. |
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