Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats

doi:10.1016/S0304-3835(00)00461-4

Cancer Letters

Volume 157, Issue 1, 31 August 2000, Pages 15-21

https://doi.org/10.1016/S0304-3835(00)00461-4 Get rights and content

Abstract

The modifying effects of dietary administration of ferulic acid (FA) on azoxymethane (AOM)-induced colon carcinogenesis were examined in three experiments with male 344 rats. In the first experiment, the modifying effect of FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm² of group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a long-term assay for the effects of FA was conducted with seven groups. At the termination (35 weeks), groups 2 and 3 which were given FA during the initiation phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone (59%; P<0.05). In the third experiment, to determine whether FA could modify the activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly elevated GST activity in liver (P<0.03), and QR activities in liver and colonic mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are related to the blocking effect of FA on AOM-induced colon carcinogenesis.

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.

Section snippets

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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Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats

Abstract

Introduction

Section snippets

Animals and diet

Results

Discussion

Acknowledgements

Cancer Lett.

Toxicology

Cancer Lett.

The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today

J. Natl. Cancer Inst.

Diet and carcinogenesis

Carcinogenesis

Chemoprevention by naturally-occurring and synthetic agents in oral, liver and large bowel carcinogenesis

J. Cell Biochem.

Dietary prevention of azoxymethane-induced colon carcinogenesis with rice-germ in F344 rats

Carcinogenesis

Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: exceptional activity of ellagic acid

Proc. Natl. Acad. Sci. USA

Plant phenolics as inhibitors of mutational and precarcinogenic events

Can. J. Physiol. Pharmacol

A hypothesis for dietary compounds as blocking agents of chemical carcinogenesis: plant phenolics and pyrrole pigments

Nutr. Cancer

Catalysis of nitrosation in vivo in rats by catechin and resorcinol and inhibition by chlorogenic acid

Carcinogenesis

Caffeic and ferulic acids as blockers of nitrosamine formation

Carcinogenesis

Inhibition of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and fertulic acids

Carcinogenesis