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 Apc(min/+) 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 beta-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 micromol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of beta-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 micromol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apc(min/+) mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear beta-catenin and activated Akt and ERK signaling.
authors.affiliation: Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
authors.forename: Jihyeung
authors.initials: J
authors.lastname: Ju
authors.forename: Jungil
authors.initials: J
authors.lastname: Hong
authors.forename: Jian-nian
authors.initials: JN
authors.lastname: Zhou
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Mousumi
authors.initials: M
authors.lastname: Bose
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Guang-yu
authors.initials: GY
authors.lastname: Yang
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hou
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.forename: Adelaide M
authors.initials: AM
authors.lastname: Carothers
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D017491:Genes, APC; D019073:HT29 Cells; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D015820:Cadherins; D051176:beta Catenin; D007975:Leukotriene B4; D002110:Caffeine; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D010741:Phospholipases A; D015232:Dinoprostone