Iron Chelation Properties of Green Tea Epigallocatechin‐3‐Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking

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.

Iron-doped zinc oxide nanoparticles-triggered elicitation of important phenolic compounds in cell cultures of Fagonia indica

“…One of the reasons for this could be that Iron (Fe) is a transition metal that forms chelates and complexes with phenolic plant secondary metabolites. It has been observed that epigallocatechin gallate acts as a robust Iron chelator (Md Nesran et al 2020 ). In our case, iron supplementation in the form of Fe-ZnO-NPs might have triggered the production of enhanced quantities of this compound to reduce the toxic effects of Iron and Zinc given in excess amounts (250 µg/ml).…”

Iron-doped zinc oxide nanoparticles-triggered elicitation of important phenolic compounds in cell cultures of Fagonia indica.

“…One of the reasons for this could be the fact that Iron (Fe) is a transition metal that forms chelates and complexes with phenolic plant secondary metabolites. It has been observed that epigallocatechin gallate acts as a robust Iron chelator (Md Nesran et al, 2020). In our case, the supplementation of iron in the form of Fe-ZnO-NPs might have triggered the production of enhanced quantities of this compound to reduce the toxic effects of Iron and Zinc given in excess amounts (250 µg/ml).…”

Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products

“…EGCG has been proven to protect pancreatic β cells against iron toxicity and erastin-induced ferroptosis through neutralizing iron and preventing GPX4 inactivation ( Kose et al, 2019 ). Moreover, EGCG can also act as an iron chelator to regulate the TFRC/FTH expression and to prevent GPX4 activation, resulting in the inhibition of ferroptosis ( Md Nesran et al, 2020 ). In addition to its antioxidative properties, EGCG is evidenced by clinical experience as an anticancer agent that modulates GPX4 levels to promote ferroptosis ( Zhu et al, 2017 ).…”