Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats
Introduction
Dietary factors play an important role for prevention of human diseases including cancer [1], [2]. We have reported different types chemopreventive agents derived from edible plants against colon carcinogenesis [3]. Very recently, we also reported that rice-germ is a promising chemopreventive agent for human large bowel cancers [4].
Ferulic acid (FA; Fig. 1) is a phenolic acid contained in plant materials such as rice, green tea, and coffee beans. Several plant phenolics are known to be potent inhibitors for mutagenesis and carcinogenesis by polycyclic aromatic hydrocarbons [5], [6]. They act as effective electrophilic trapping agents [7] and are also known to be blockers of nitrosamine formation [8], [9]. We have reported an inhibitory effect of FA on 4-nitroquinoline 1-oxide (4-QO)-induced rat tongue carcinogenesis [10]. FA has also been reported to depress TPA-promotion of skin tumorigenesis [11] as well as to inhibit occurrence of pulmonary cancers in mice [12]. In the present study, chemopreventive potentials of FA on azoxymethane (AOM)-induced colon carcinogenesis were examined in rats. Since, certain chemopreventive agents are known to increase activities of detoxifying enzymes [13], the activities of glutathione S-transferase (GST) and quinone reductase (QR) were also assessed in the liver and colonic mucosa.
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Animals and diet
Male F344 rats (Shizuoka Laboratory Animals Center, Shizuoka, Japan), 4-weeks-old, were used. All animals were housed in wire cages (three or four rats/cage) with free access to the drinking water and basal diet, CE-2 (CLEA Japan Inc., Tokyo, Japan), under controlled conditions of humidity (50±10%), lighting (12 h light/dark cycle) and temperature (23±2°C). CE-2 diet contained 45.5% crude carbohydrate, 24.8% crude protein, 4.6% crude fat, 7.2% ash, 4.2% crude cellulose, 3.9% minerals, 1%
Results
In this study, dietary administration of FA caused no clinical signs for toxicity, low survival, poor condition, or histological changes suggesting toxicity in the liver, kidney, and lung. There were no significant differences in the average body weights or liver weights among the groups (data not shown). Findings for ACF in the first experiment are summarized in Table 1. Colonic ACF were detected only in rats treated with AOM (groups 1–3). The total number of ACF/colon in group 2 or 3 was
Discussion
Feeding of FA prevented the development of ACF (number of ACF/colon), as revealed by quantification of ACF in the first experiment. Such data with FA on AOM-induced colonic ACF suggest that the biomarker is useful, particularly for screening blocking chemopreventive agents on carcinogenesis [20]. These results also suggest that FA inhibits the growth of colonic ACF and suppresses progression of preneoplasia to malignant neoplasia. In this study, the second experiment was conducted on the basis
Acknowledgements
We would like to thank Kyoko Takahashi and Chikako Usui for technical assistance, Ayumu Nagata for secretarial assistance, and Kazumasa Satoh for animal care. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan, and the program for Promotion of Fundamental Studies in Health Science from the Organization for Pharmaceutical Safety and Research (OPSR), Japan.
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