title: Peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) potently suppresses dextran sulfate sodium-induced colitis and colon tumorigenesis in mice.
abstract: Previous studies reported that peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) has antiproliferative and anti-inflammatory activities. Here, we evaluated the chemopreventive effects and underlying molecular mechanisms of dietary administration of AcEGCG and EGCG in dextran sulfate sodium (DSS)-induced colitis in mice. The mice were fed a diet supplemented with either AcEGCG or EGCG prior to DSS induction. Our results indicated that AcEGCG administration was more effective than EGCG in preventing the shortening of colon length and the formation of aberrant crypt foci (ACF) and lymphoid nodules (LN) in mouse colon stimulated by DSS. Our study observes that AcEGCG treatment inhibited histone 3 lysine 9 (H3K9) acetylation but did not affect histone acetyltransferase (HAT) activity and acetyl- CREB-binding protein (CBP)/p300 levels. In addition, pretreatment with AcEGCG decreased the proinflammatory mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation and p65 acetylation. We also found that treatment with AcEGCG increased heme oxygenase-1(HO-1) expression via activation of extracellular signal-regulated protein kinase (ERK)1/2 signaling and acetylation of NF-E2-related factor 2 (Nrf2), thereby abating DSS-induced colitis. Moreover, dietary feeding with AcEGCG markedly reduced colitis-driven colon cancer in mice. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary AcEGCG against inflammatory bowel disease (IBD) and potentially colon cancer associated with colitis. These findings provide insight into the biological actions of AcEGCG and might establish a molecular basis for the development of new cancer chemopreventive agents.
authors.affiliation: Department of Seafood Science, National Kaohsiung Marine University, Nanzih District, Kaohsiung, Taiwan.
authors.forename: Yi-Shiou
authors.initials: YS
authors.lastname: Chiou
authors.forename: Nianhan Jia-Lin
authors.initials: NJ
authors.lastname: Ma
authors.forename: Shengmin
authors.initials: S
authors.lastname: Sang
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Ying-Jan
authors.initials: YJ
authors.lastname: Wang
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000107:Acetylation; D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011292:Premedication; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000085:Acetates; C516941:peracetylated epigallocatechin-3-gallate; D002392:Catechin; D016264:Dextran Sulfate; C045651:epigallocatechin gallate