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

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 Apc^Min mouse model. For the first group of mice, 100 μg BaP/kg bw was administered to mice in peanut oil via oral gavage over a 60 day period. For the second group, RVT was co-administered with BaP at a dose of 45 μg/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 & RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology. Resveratrol reduced the number of colon adenomas in BaP + RVT-treated mice significantly compared to 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 post treatment with RVT and BaP. Co-treatment 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.