Chemoprevention of benzo(a)pyrene-induced colon polyps in ApcMin mice by resveratrol

被引:32
作者
Huderson, Ashley C. [1 ]
Myers, Jeremy N. [1 ]
Niaz, Mohammad S. [1 ]
Washington, Mary K. [2 ]
Ramesh, Aramandla [1 ]
机构
[1] Meharry Med Coll, Dept Biochem & Canc Biol, Nashville, TN 37208 USA
[2] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA
关键词
Benzo(a)pyrene; Polycyclic aromatic hydrocarbons; Resveratrol; Colon carcinogenesis; Apc(Min) mouse; POLYCYCLIC AROMATIC-HYDROCARBONS; ABERRANT CRYPT FOCI; CELL-CYCLE ARREST; AGENT RESVERATROL; DNA-DAMAGE; TRANS-RESVERATROL; INTESTINAL TUMORIGENESIS; COLORECTAL-CANCER; EPITHELIAL-CELLS; TUMOR-GROWTH;
D O I
10.1016/j.jnutbio.2012.04.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human dietary exposure to benzo(a)pyrene (BaP) has generated interest with regard to the association of BaP with gastrointestinal carcinogenesis. Since colon cancer ranks third among cancer-related mortalities, it is necessary to evaluate the effect of phytochemicals on colon cancer initiation and progression. In this study, we investigated the preventive effects of resveratrol (RVT) on BaP-induced colon carcinogenesis in Aix(Min) mouse model. For the first group of mice, 100 mu g BaP/kg body weight was administered to mice in peanut oil via oral gavage over a 60-day period. For the second group, RVT was coadministered with BaP at a dose of 45 mu g/kg. For the third group, RVT was administered for 1 week prior to BaP exposure for 60 days. Jejunum, colon and liver were collected at 60 days post BaP and RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology. RVT reduced the number of colon adenomas in BaP+RVT-treated mice significantly compared to that in mice that received BaP alone. While dysplasia of varying degrees was noted in colon of BaP-treated mice, the dysplasias were of limited occurrence in RVT-treated mice. To ascertain whether the tumor inhibition is a result of altered BaP-induced toxicity of tumor cells, growth, apoptosis and proliferation of adenocarcinoma cells were assessed posttreatment with RVT and BaP. Cotreatment with RVT increased apoptosis and decreased cell proliferation to a greater extent than with BaP alone. Overall, our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP and holds promise as a therapeutic agent. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:713 / 724
页数:12
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