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Fulltext Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α

Md Nesran ZN, Shafie NH, Ishak AH, Mohd Esa N, Ismail A, Md Tohid SF

Biomed Res Int, 2019;2019:3480569.
PMID: 31930117 DOI: 10.1155/2019/3480569

Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1α). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.
Fulltext Iron Chelation Properties of Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Analysis on Tfr/Fth Regulations and Molecular Docking

Md Nesran ZN, Shafie NH, Md Tohid SF, Norhaizan ME, Ismail A

Evid Based Complement Alternat Med, 2020;2020:7958041.
PMID: 32280356 DOI: 10.1155/2020/7958041

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.
Fulltext Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach

Hanafiah A, Abd Aziz SNA, Md Nesran ZN, Wezen XC, Ahmad MF

Heliyon, 2024 Mar 30;10(6):e28128.
PMID: 38533069 DOI: 10.1016/j.heliyon.2024.e28128

The impact of H. pylori resistance on patient's treatment failure is a major concern. Therefore, the development of novel or alternative therapies for H. pylori is urgently needed. The purpose of this study was to investigate the molecular interactions of various antimicrobial peptides (AMPs) to H. pylori proteins. We performed the peptide-protein molecular docking using HADDOCK 2.4 webserver. Fourteen AMPs were tested for their binding efficacy against four H. pylori proteins. Simulation of the peptide-protein complex was performed using molecular dynamic software package AMBER20. From molecular docking analysis, five peptides (LL-37, Tilapia piscidin 4, napin, snakin-1 and EcAMP1) showed strong binding interactions against H. pylori proteins. The strongest binding affinity was observed in the interactions between Snakin-1 and PBP2, TP4 and type I HopQ and EcAMP1 and type I HopQ with -11.1, -13.6 and -13.8 kcal/mol, respectively. The dynamic simulation was performed for two complexes (snakin1-PBP2 and EcAMP1-HopQ). Results of the dynamics simulation showed that EcAMP1 had stable interaction and binding to type I HopQ protein without significant structural changes. In conclusion, both results of docking and simulation showed that EcAMP1 might be useful as a potential therapeutic agent for H. pylori treatment. This molecular approach provides deep understanding of the interaction insights between AMPs and H. pylori proteins. It paves the way for the development of novel anti-H. pylori using antimicrobial peptides.
Fulltext Efficacy of decision aid delivery modes in prostate cancer screening: umbrella review and network meta-analysis

Ang ZY, Kong YL, Md Nesran ZN, Lee SWH

BJU Int, 2025 Feb;135(2):222-234.
PMID: 39402746 DOI: 10.1111/bju.16545

OBJECTIVE: To review and compare the efficacy of different delivery modes of decision aids (DAs), including computer-based, print-based, multimedia-based, video-based, and website-based on decision-making outcomes for prostate cancer screening compared to usual care (UC) and among the delivery modes.
METHODS: PubMed, the Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Advanced Search, and Turning Research Into Practice (TRIP) Database were systematically searched from inception to August 2023. The primary outcomes were knowledge level, knowledge scores, participation in shared decision-making (SDM), decisional conflict, and preference for SDM participation. Secondary outcomes were the proportion of subjects who underwent screening (actual screening utilisation) and the proportion of subjects who intended to be screened (intention to undergo screening). Network and pairwise meta-analyses were performed using random-effects models.
RESULTS: Seven systematic reviews were included. Network meta-analysis found that multimedia (relative risk [RR] 1.51, 95% confidence interval [CI] 1.02-2.24), print (RR 1.82, 95% CI 1.23-2.69), and website-based (RR 1.99, 95% CI 1.32-3.01) DAs significantly increased participation in SDM compared to the computer-based DA. There was a significant reduction in the actual screening utilisation in the computer DA arm compared to the other delivery modes. No significant differences between all delivery modes were noted on knowledge levels, knowledge scores, decisional conflict, preference for SDM participation, and intention to undergo screening. The highest mean surface under the cumulative ranking curve for all primary outcomes showed that website-based was the most effective delivery mode, followed by print-based DA. The pairwise meta-analysis showed a significant increase in participants' knowledge level, knowledge scores, a reduced intention to undergo screening and actual screening utilisation compared to UC.
CONCLUSIONS: The findings suggest that different types of DAs have varying levels of effectiveness in increasing knowledge level, knowledge scores, participation in SDM, and influencing screening behaviours. While website-based DA appeared the most effective, employing the print-based DA could be a practical solution in settings with limited resources.