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Dietary‐feeding of grape seed extract prevents azoxymethane‐induced colonic aberrant crypt foci formation in fischer 344 rats
Author(s) -
Velmurugan Balaiya,
Singh Rana P.,
Agarwal Rajesh,
Agarwal Chapla
Publication year - 2010
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20643
Subject(s) - azoxymethane , aberrant crypt foci , grape seed extract , biology , apoptosis , survivin , crypt , colorectal cancer , cell growth , cyclin d1 , cancer research , carcinogenesis , medicine , endocrinology , cancer , cell cycle , pathology , biochemistry , colonic disease , genetics , alternative medicine
Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)‐induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six‐week‐old rats were injected with AOM, and fed control diet or the one supplemented with 0.25% or 0.5% (w/w) GSE in pre‐ and post‐AOM or only post‐AOM experimental protocols. At 16 wk of age, rats were sacrificed and colons were evaluated for ACF formation followed by cell proliferation, apoptosis, and molecular analyses by immunohistochemistry. GSE‐feeding caused strong chemopreventive efficacy against AOM‐induced ACF formation in terms of up to 60% ( P < 0.001) reduction in number of ACF and 66% ( P < 0.001) reduction in crypt multiplicity. Mechanistic studies showed that GSE‐feeding inhibited AOM‐induced cell proliferation but enhanced apoptosis in colon including ACF, together with a strong decrease in cyclin D1, COX‐2, iNOS, and survivin levels. Additional studies showed that GSE‐feeding also decreased AOM‐caused increase in β‐catenin and NF‐κB levels in colon tissues. Compared to control animals, GSE alone treatment did not show any considerable change in these biological and molecular events in colon, and was nontoxic. Together, these findings show the chemopreventive efficacy of GSE against the early steps of colon carcinogenesis in rats via likely targeting of β‐catenin and NF‐κB signaling, and suggest its potential usefulness for the prevention of human CRC. © 2010 Wiley‐Liss, Inc.