Abstract
In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (−7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71; two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.
Highlights
Since 500 000 years, China and Japan, in particular, have been consuming green tea on a daily basis to the extent of making green tea as health treatment purpose [1]. e green tea, known scientifically as Camellia sinensis L, is rooted in tea plants
The treatment of EGCG had caused transferrin receptor (TfR) being upregulated and FtH being downregulated, indicating that iron chelation activity had occurred in the HT-29
Iron chelation occurrence in HT-29 was determined by the upregulation of the transferrin receptor (TfR)
Summary
Since 500 000 years, China and Japan, in particular, have been consuming green tea on a daily basis to the extent of making green tea as health treatment purpose [1]. e green tea, known scientifically as Camellia sinensis L, is rooted in tea plants. EGCG has demonstrated as the most effective polyphenol in green tea as a chemopreventive agent. It has antiproliferative effects over colorectal cancer cell lines SW480 and HCT-116 by induction of apoptosis [7]. Many evidences have demonstrated that treatment of cells with an iron chelator will increase TfR mRNA levels and TfR protein expression [15, 16]. DFO is known as an iron chelator which is able to cause apoptosis in colon cancer cells [18]. It is a membranepermeable chelator, and these characteristics explain its iron deprivation activity in cancer cells [19]. It is a membranepermeable chelator, and these characteristics explain its iron deprivation activity in cancer cells [19]. e efficacy of DFO in minimalizing Fe-based cytotoxicity has made it as a potential candidate to be considered as an anticancer agent [20]
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