Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea

Jihyeung Ju, Jungil Hong, Jian Nian Zhou, Zui Pan, Mousumi Bose, Jie Liao, Guang Yu Yang, Ying Ying Liu, Zhe Hou, Yong Lin, Jianjie Ma, Weichung Joe Shih, Adelaide M. Carothers, Chung S. Yang

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Abstract

The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apcmin/+ mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a dose of 0.044% in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02% to 0.32%. P.O. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear β-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 μmol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of β-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 μmol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apcmin/+ mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear β-catenin and activated Akt and ERK signaling.

Original languageEnglish
Pages (from-to)10623-10631
Number of pages9
JournalCancer Research
Volume65
Issue number22
DOIs
StatePublished - 15 Nov 2005

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Catechin
Tea
Carcinogenesis
Catenins
Cadherins
Caffeine
Drinking
Intestinal Neoplasms
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Cyclin D1
epigallocatechin gallate
Colonic Neoplasms
Neoplasms
Cytoplasm
Cell Membrane

Cite this

Ju, Jihyeung ; Hong, Jungil ; Zhou, Jian Nian ; Pan, Zui ; Bose, Mousumi ; Liao, Jie ; Yang, Guang Yu ; Liu, Ying Ying ; Hou, Zhe ; Lin, Yong ; Ma, Jianjie ; Shih, Weichung Joe ; Carothers, Adelaide M. ; Yang, Chung S. / Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea. In: Cancer Research. 2005 ; Vol. 65, No. 22. pp. 10623-10631.
@article{3517fa1fa76046de8ad68620635af7d3,
title = "Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea",
abstract = "The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apcmin/+ mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08{\%} or 0.16{\%} in drinking fluid significantly decreased small intestinal tumor formation by 37{\%} or 47{\%}, respectively, whereas caffeine at a dose of 0.044{\%} in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02{\%} to 0.32{\%}. P.O. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear β-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 μmol/L at different times) also increased protein levels of E-cadherin by 27{\%} to 58{\%}, induced the translocation of β-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 μmol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apcmin/+ mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear β-catenin and activated Akt and ERK signaling.",
author = "Jihyeung Ju and Jungil Hong and Zhou, {Jian Nian} and Zui Pan and Mousumi Bose and Jie Liao and Yang, {Guang Yu} and Liu, {Ying Ying} and Zhe Hou and Yong Lin and Jianjie Ma and Shih, {Weichung Joe} and Carothers, {Adelaide M.} and Yang, {Chung S.}",
year = "2005",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-05-1949",
language = "English",
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pages = "10623--10631",
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Ju, J, Hong, J, Zhou, JN, Pan, Z, Bose, M, Liao, J, Yang, GY, Liu, YY, Hou, Z, Lin, Y, Ma, J, Shih, WJ, Carothers, AM & Yang, CS 2005, 'Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea', Cancer Research, vol. 65, no. 22, pp. 10623-10631. https://doi.org/10.1158/0008-5472.CAN-05-1949

Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea. / Ju, Jihyeung; Hong, Jungil; Zhou, Jian Nian; Pan, Zui; Bose, Mousumi; Liao, Jie; Yang, Guang Yu; Liu, Ying Ying; Hou, Zhe; Lin, Yong; Ma, Jianjie; Shih, Weichung Joe; Carothers, Adelaide M.; Yang, Chung S.

In: Cancer Research, Vol. 65, No. 22, 15.11.2005, p. 10623-10631.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea

AU - Ju, Jihyeung

AU - Hong, Jungil

AU - Zhou, Jian Nian

AU - Pan, Zui

AU - Bose, Mousumi

AU - Liao, Jie

AU - Yang, Guang Yu

AU - Liu, Ying Ying

AU - Hou, Zhe

AU - Lin, Yong

AU - Ma, Jianjie

AU - Shih, Weichung Joe

AU - Carothers, Adelaide M.

AU - Yang, Chung S.

PY - 2005/11/15

Y1 - 2005/11/15

N2 - The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apcmin/+ mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a dose of 0.044% in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02% to 0.32%. P.O. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear β-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 μmol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of β-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 μmol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apcmin/+ mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear β-catenin and activated Akt and ERK signaling.

AB - The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apcmin/+ mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a dose of 0.044% in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02% to 0.32%. P.O. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear β-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 μmol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of β-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 μmol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apcmin/+ mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear β-catenin and activated Akt and ERK signaling.

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U2 - 10.1158/0008-5472.CAN-05-1949

DO - 10.1158/0008-5472.CAN-05-1949

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EP - 10631

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JF - Cancer Research

SN - 0008-5472

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