(−)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells

Le Ying, Feng Yan, Bryan R.G. Williams, Ping Xu, Xin Li, Yueling Zhao, Yiqun Hu, Yuefei Wang, Dakang Xu, Jing Dai

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumour activities for cancer chemoprevention. The mechanism of anti-tumour effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homologue 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal. Different human CRC cell lines exhibited differing expression of levels of the EZH2 protein. In RKO cells, EGCG and the EZH2 inhibitor GSK343 exhibited similar inhibitory efficacy on the proliferation, invasion and migration abilities of the cells, and suppressed protein expression of trimethylated lysine 27 on histone H3 (H3K27me3), which may be caused by the loss of the enzymatic function of EZH2. EGCG and GSK343 were found to have a synergistic effect on the growth of RKO cells in lower concentrations. EZH2-correlated genes were enriched in the cell cycle pathway, the top-ranking up-regulated pathway in tumour tissues, based on pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalClinical and Experimental Pharmacology and Physiology
Volume45
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • cell cycle
  • colorectal cancer
  • EGCG
  • EZH2

Cite this

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title = "(−)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells",
abstract = "Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumour activities for cancer chemoprevention. The mechanism of anti-tumour effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homologue 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal. Different human CRC cell lines exhibited differing expression of levels of the EZH2 protein. In RKO cells, EGCG and the EZH2 inhibitor GSK343 exhibited similar inhibitory efficacy on the proliferation, invasion and migration abilities of the cells, and suppressed protein expression of trimethylated lysine 27 on histone H3 (H3K27me3), which may be caused by the loss of the enzymatic function of EZH2. EGCG and GSK343 were found to have a synergistic effect on the growth of RKO cells in lower concentrations. EZH2-correlated genes were enriched in the cell cycle pathway, the top-ranking up-regulated pathway in tumour tissues, based on pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells.",
keywords = "cell cycle, colorectal cancer, EGCG, EZH2",
author = "Le Ying and Feng Yan and Williams, {Bryan R.G.} and Ping Xu and Xin Li and Yueling Zhao and Yiqun Hu and Yuefei Wang and Dakang Xu and Jing Dai",
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(−)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells. / Ying, Le; Yan, Feng; Williams, Bryan R.G.; Xu, Ping; Li, Xin; Zhao, Yueling; Hu, Yiqun; Wang, Yuefei; Xu, Dakang; Dai, Jing.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 45, No. 1, 01.01.2018, p. 58-67.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - (−)-Epigallocatechin-3-gallate and EZH2 inhibitor GSK343 have similar inhibitory effects and mechanisms of action on colorectal cancer cells

AU - Ying, Le

AU - Yan, Feng

AU - Williams, Bryan R.G.

AU - Xu, Ping

AU - Li, Xin

AU - Zhao, Yueling

AU - Hu, Yiqun

AU - Wang, Yuefei

AU - Xu, Dakang

AU - Dai, Jing

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumour activities for cancer chemoprevention. The mechanism of anti-tumour effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homologue 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal. Different human CRC cell lines exhibited differing expression of levels of the EZH2 protein. In RKO cells, EGCG and the EZH2 inhibitor GSK343 exhibited similar inhibitory efficacy on the proliferation, invasion and migration abilities of the cells, and suppressed protein expression of trimethylated lysine 27 on histone H3 (H3K27me3), which may be caused by the loss of the enzymatic function of EZH2. EGCG and GSK343 were found to have a synergistic effect on the growth of RKO cells in lower concentrations. EZH2-correlated genes were enriched in the cell cycle pathway, the top-ranking up-regulated pathway in tumour tissues, based on pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells.

AB - Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumour activities for cancer chemoprevention. The mechanism of anti-tumour effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homologue 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal. Different human CRC cell lines exhibited differing expression of levels of the EZH2 protein. In RKO cells, EGCG and the EZH2 inhibitor GSK343 exhibited similar inhibitory efficacy on the proliferation, invasion and migration abilities of the cells, and suppressed protein expression of trimethylated lysine 27 on histone H3 (H3K27me3), which may be caused by the loss of the enzymatic function of EZH2. EGCG and GSK343 were found to have a synergistic effect on the growth of RKO cells in lower concentrations. EZH2-correlated genes were enriched in the cell cycle pathway, the top-ranking up-regulated pathway in tumour tissues, based on pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). In accord with this, we confirmed that EGCG and GSK343 could both significantly arrest the G0/G1 phase in RKO cell cycle, suggesting EGCG and EZH2 inhibitor share a common mechanism of action in RKO cells.

KW - cell cycle

KW - colorectal cancer

KW - EGCG

KW - EZH2

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U2 - 10.1111/1440-1681.12854

DO - 10.1111/1440-1681.12854

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