Inhibition Of Colon Carcinogenesis Research Articles

Dry Beans Inhibit Azoxymethane-Induced Colon Carcinogenesis in F344 Rats

Epidemiological studies show a low incidence of colon cancer in many Latin American countries where the consumption of dry beans (e.g., pinto) is high. The purpose of this study was to use rats as an animal model to obtain experimental data on the inhibition of colon carcinogenesis by dry beans. Fifty-three 5-wk-old weanling male F344 rats were randomly assigned by weight to the following groups: control (11 rats), casein diet (21 rats), and bean diet (21 rats). Animals fed the casein and bean diets were treated with the carcinogen azoxymethane (AOM) once weekly for 2 wk. Rats in the control group also consumed the casein diet but were not exposed to AOM. All diets were isocaloric. The protein concentration of the diets was adjusted to 18 g/100 g with casein, and the fat concentration was adjusted to 5 g/100 g with corn oil. Rats fed the bean diet had significantly fewer colon adenocarcinomas (P< 0.05) than rats fed the casein diet (5 vs. 22 tumors), and significantly fewer rats fed the bean diet (P< 0.05) had colonic tumors than did casein-fed rats (24 vs. 50%). Tumor multiplicity was also significantly lower for the bean-fed rats, and significantly fewer (P< 0.05) tumors per tumor-bearing rat were observed in bean-fed rats than in casein-fed rats (1.0 ± 0.0 vs. 2.5 ± 0.6). This study demonstrates that dry beans contain anticarcinogenic compounds capable of inhibiting AOM-induced colon cancer in rats. However, the specific anticarcinogenic components within dry beans have not been identified, and it is unclear whether dietary fiber, phytochemicals or other components within dry beans are primarily responsible for the anticarcinogenic properties of beans.

Abstract 2343: Fecal metabolic changes following rice bran supplementation in the murine model for colitis associated cancer of the colon

Abstract Dietary rice bran mediated inhibition of colon carcinogenesis has been described via multiple mechanisms including, but not limited to, reduced cell proliferation, induction of apoptosis and modulation of arachidonic acid metabolism. Human clinical research further supports rice bran modulation of gut microbiome metabolism for enhancing colonic health. Little is known regarding the time series of fecal metabolite changes involved in the progression of colon cancer in Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) treated mice and modulation of metabolic pathways by dietary rice bran supplementation. This study investigated the metabolic changes associated with rice bran supplementation during colitis-associated cancer over 14 weeks. Conventional adult male BALB/c mice were fed control diet (AIN93) or 10% w/w rice bran diet during AOM-DSS treatment. Global, non-targeted metabolomics was applied to murine fecal samples following consumption of rice bran after 2 days, 2, 6, 10 and 14 weeks and compared to mice fed control diet. Raw data was extracted, peak-identified and processed using Metabolon's hardware and software. A total of 702 biochemicals, 592 compounds of known identity and 110 compounds of unknown structural identity were reported, and ANOVA contrasts used to identify biochemicals that differed significantly between experimental groups. Random forest analysis based on an ensemble of decision trees revealed dietary distinctions in 30 metabolites at 10wk and 14wk with a predictive accuracy of 92% and 75%, respectively. These included vitamins, thiamine (vitamin B1), retinol (vitamin A) pyridoxine (vitamin B6), pyridoxal and pyridoxate) and cofactors, quinolinate, 1-methylnicotinamide and trigonelline, with therapeutic, antioxidant and anti-inflammatory properties. There was also fold-increases in rice bran-derived phenolics, namely 2-hydroxyhippuarte, 3-(3-hydroxyphenyl)propionate and 3-phenylpropionate at both 10 and 14 weeks when compared to control. The bioavailability of these bioactive phenolic compounds was further supported by colonic tissue metabolite profiling. Shifts in cellular energy metabolism, shown by citrate, aconitate, and malate; and in lipid metabolites namely (glycerol 3-phosphate, monoacylglycerols (1-oleoylglycerol (18:1) and 2-linoleoylglycerol (18:1)) and diacylglycerols (palmitoyl-linoleoyl-glycerol (16:0/18:2) and oleoyl-linoleoyl-glycerol (18:1/18:2) were detected as novel mechanisms for rice bran mediated-inhibition of colon cancer. TCA cycle metabolites may reflect the favorably altered intestinal microenvironment for depletion of cancer cells. This study supports a time series of fecal metabolic profiles associated with dietary rice bran alongside identification of novel mechanism(s) by which rice bran protects against or prevents progression of colon cancer. Citation Format: Petronella R. Hove, Annika Weber, Bridget Baxter, Hend Ibrahim, Kristopher Parker, Komal Raina, Elizabeth P. Ryan. Fecal metabolic changes following rice bran supplementation in the murine model for colitis associated cancer of the colon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2343.

Induction of endoplasmic reticulum stress and inhibition of colon carcinogenesis by the anti-helmintic drug rafoxanide.

Colorectal cancer (CRC) remains one of the leading causes of mortality worldwide. Drug repositioning is a promising approach for new cancer therapies, as it provides the opportunity to rapidly advance potentially promising agents into clinical trials. The FDA-approved anti-helminthic drug rafoxanide was recently reported to antagonize the oncogenic function of the BRAF V600E mutant protein, commonly found in CRCs, as well as to inhibit the proliferation of skin cancer cells. These observations prompted us to investigate the potential anti-cancer effects of rafoxanide in CRC models. We found rafoxanide inhibited proliferation in CRC cells, but not in normal colonic epithelial cells. Rafoxanide's anti-proliferative action was associated with marked reduction in cyclin D1 protein levels and accumulation of cells in the G0/G1 phase. These effects relied on selective induction of the endoplasmic reticulum stress (ERS) response in CRC cells and were followed by caspase-dependent cell death. Systemic administration of rafoxanide to Apcmin/+ mice induced to develop CRCs caused ERS activation, proliferation inhibition and apoptosis induction in the neoplastic cells. Collectively, our data suggest rafoxanide might be repurposed as an anti-cancer drug for the treatment of CRC.

Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs

The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated.

N-3 polyunsaturated fatty acids reverse the development of polyps in Apc(Min/+) transgenic mice.

Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) have been demonstrated to reduce tumor load in Apc(Min/+) mice, supporting a role for n-3 PUFAs in the inhibition of colon carcinogenesis and progression. The aim of the present study was to investigate whether a diet enriched with n-3 PUFAs, known already to have anti-neoplastic efficacy in Apc(Min/+) mice, would reverse the development of intestinal polyps. For this purpose, Apc(Min/+) mice were randomly divided into 3 groups of 5 animal each and fed as follows: control ST1 and ST2 groups, received a purified AIN-93M standard diet for 5 and 10 weeks, respectively; the OM-3R group received a purified AIN-93M standard diet for 5 weeks and a diet supplemented with salmon oil, rich in n-3 PUFAs, for another 5 weeks. After dietary treatment, in intestinal tissue, we evaluated the polyp number and volume, expression levels of cell proliferation- and apoptosis-related proteins, as well as the protein expression of LDL receptor and the levels of fatty acid synthase (FAS) activity. The results showed the ability of a diet enriched with n-3 PUFAs to suppress intestinal polyps in Apc(Min/+) mice, and to significantly reverse polyp development associated with the downregulation of cell proliferation markers and with the induction of estrogen receptor β and LDL receptor, which are negative modulators of cellular proliferation. This noteworthy finding is important for a translational study evaluating the therapeutic role of n-3 PUFAs in the prevention and treatment of subjects with gastrointestinal diseases.

Inhibition of colon carcinogenesis by 5‐demethylnobiletin in azoxymethane‐treated rats

We previously demonstrated that 5-demethylnobiletin (5DN, a unique citrus flavonoid) had potent anticancer effects in both cell culture and mouse models of colon carcinogenesis. In this study, we d...

Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol

PurposeColon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. MethodsProliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [3H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice. ResultsCBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer. ConclusionsCBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.

Inhibition of Colon Carcinogenesis by 2-Methoxy-5-Amino-N-Hydroxybenzamide, a Novel Derivative of Mesalamine

Mesalamine has been reported to protect against inflammatory bowel disease-related colorectal cancer (CRC), but several drug-related issues have limited its use in chemopreventive programs. We evaluated the antineoplastic properties of mesalamine derivatives using in vitro and in vivo models of CRC. CRC cell proliferation and cell-cycle progression were evaluated by flow cytometry after exposure to mesalamine or mesalamine derivatives. Cyclins, cyclin-dependent kinases, and endoplasmic reticulum stress-related molecules were examined by immunoblotting. The in vivo antineoplastic effect of 2-methoxy-5-amino-N-hydroxybenzamide (2-14) was evaluated in a syngenic, CT26-derived xenograft mouse model of CRC and in the azoxymethane/dextran sulfate sodium-induced mouse model of colitis-associated CRC. The mesalamine derivative 2-14 was 10-fold more potent than mesalamine in inhibiting CRC cell proliferation. After exposure to 2-14, cyclin D1 expression was reduced and G0/G1 phase cells accumulated. These events were preceded by activation of eukaryotic translation initiation factor 2-alpha kinase 3 (pancreatic endoplasmic reticulum eIF2alpha kinase), phosphorylation of eukaryotic translation initiation factor 2alpha, induction of activating transcription factor 4, and splicing of X-box binding protein 1 messenger RNA, events that define endoplasmic reticulum stress. Silencing of PERK restored cyclin D1 levels, allowing cells to overcome the cell-cycle block induced by 2-14. Mice injected with 2-14 developed fewer CRC xenograft-derived tumors. Moreover, 2-14 injection reduced the development of neoplastic lesions induced by azoxymethane and dextran sulfate sodium in mice. The mesalamine derivative 2-14 inhibited CRC cell proliferation in vitro and prevented CRC progression in mouse models.

Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethane-treated F344 rats

Green tea and its constituents have shown cancer-preventive activities in many animal models. In order to prepare for a human trial on the inhibition of colon carcinogenesis, we conducted a study with green tea polyphenols as the preventive agent in an azoxymethane (AOM)-induced rat colon cancer model using aberrant crypt foci (ACF) as an end point. F344 rats were given two weekly injections of AOM (15 mg/kg), and then fed a 20% high-fat diet with or without 0.12 or 0.24% Polyphenon E (PPE, a standardized green tea preparation consisting 65% of (-)-epigallocatechin-3-gallate and 22% of other catechins) for 8 weeks. Colorectal ACF were analyzed under a microscope after methylene blue staining. Dietary PPE administration was found to significantly and dose dependently decrease the total number of ACF per rat and the total number of aberrant crypt per rat. Moreover, treatment with 0.24% PPE also significantly decreased the percentage of large ACF (four or more crypts) and the percentage of ACF with high-grade dysplasia in total ACF. The high-grade dysplastic ACF from 0.24% PPE-treated group had increased apoptosis and decreased nuclear expression levels of beta-catenin and cyclin D1. Retinoid X receptor (RXR)alpha expression was reduced in high-grade dysplastic ACF, adenoma and adenocarcinoma during AOM-induced colon carcinogenesis, and the PPE treatment partially prevented the loss of RXRalpha expression in high-grade dysplastic ACF. Taken together, our results strongly suggest the colon cancer-preventive activity of PPE and identified possible molecular markers for future colon cancer prevention studies.

Inhibition of Colon Carcinogenesis by Dietary Non-Nutritive Compounds

Dietary habit is instrumental in about 50% of human colorectal cancers. Consumption of fruits and vegetables is associated with decreased risk of several types of cancer, including colorectal malignancy. These foods contain many non-nutritive as well as nutritive compounds, such as carotenoids, dithiolthiones, flavonoids, glucosinolates, indoles, isothiocyanates, monoterpenes, phenols, sterols, sulfhydryls and vitamins (including C, E and folate). There may be other unknown non-nutritive constituents in foods that can reduce development. Studies using experimental chemical carcinogenesis models have indicated that several non-nutritive components, belonging to different chemical groups, in foods protect against certain types of cancer, including colorectal neoplasm. Many of these chemicals are known as potential cancer chemopreventive agents and are antioxidants that suppress carcinogenesis by (i) inhibiting phase I enzymes or blocking carcinogen formation, (ii) induction of phase II (detoxification) enzymes, (iii) scavenging DNA reactive agents, (iv) modulation of hormone homeostasis, (v) suppression of hyper-cell proliferation induced by carcinogen, (vi) induction of apoptosis, (vii) depression of tumor angiogenesis, and/or (viii) inhibition of certain phenotypic expressions of preneoplastic and neoplastic cells. Given the definite increase in the increase of colorectal cancer, we should determine the most effective mean of prevention and understand the mechanism(s) underlying successful prevention. There are critical interrelationships between diet, environmental factors and genetics that can affect risk. However, non-nutritive compounds in fruits, vegetables and other dietary constituents (teas, spices and herbs) consumed as part of the diet have the ability to reduce occurrence in pre-clinical animal carcinogenesis models. Although epidemiologic studies show similar associations, there have been very few intervention studies to date. This article describes our recent studies to determine whether several naturally occurring non-nutritive products from edible plants have any effective chemopreventive effects on colorectal carcinogenesis in rodents.

Prevention of Azoxymethane-Induced Colon Cancer by Combination of Low Doses of Atorvastatin, Aspirin, and Celecoxib in F 344 Rats

Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon adenocarcinomas. Low doses of these agents in combination inhibited colon carcinogenesis more effectively than when they were given individually at higher doses. Inhibition of colon carcinogenesis by these agents is associated with the inhibition of cell proliferation and increase in apoptosis in colon tumors. These observations are of clinical significance because this can pave the way for the use of combinations of these agents in small doses against colon cancer.

Omega-3 fatty acids in colorectal cancer prevention.

Omega-3 fatty acids in colorectal cancer prevention.

Inhibition of Colonic Aberrant Crypt Foci by Curcuminin Rats Is Affected by Age

Curcumin has antioxidative, anti-inflammatory, and chemopreventive activities. To determine whether aging affects the inhibition of colon carcinogenesis by curcumin, young (6 wk), mature (12 mo), and old (22 mo) F344 male rats were fed either AIN-93 containing 0.6% curcumin or AIN-93 control diet. Aberrant crypt foci (ACF) were induced with two weekly s.c. injections of azoxymethane. After an additional 3 mo on the diets, the number, multiplicity, and distribution of ACF were evaluated. Addition of curcumin to the diet reduced the number of ACF by 49% in young rats and by 55% in old rats (P < 0.05). However, interestingly, no reduction of ACF was found in mature rats fed curcumin. Inhibition of large ACF was also affected by age, with the greatest reduction of large ACF occurring in old rats. However, animal age did not significantly alter the effect of dietary curcumin on reduction of cyclooxygenase-2 mRNA expression in the liver or reduction of serum total cholesterol levels. These results indicate that age may play a significant role in the efficacy of chemoprevention of colon cancer by curcumin.

Cancer prevention by bovine lactoferrin and underlying mechanisms--a review of experimental and clinical studies.

In experimental studies, bovine lactoferrin (bLF) has been found to significantly inhibit colon, esophagus, lung, and bladder carcinogenesis in rats when administered orally in the post-initiation stage. Furthermore, concomitant administration with carcinogens resulted in inhibition of colon carcinogenesis, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2), which is preferentially induced by carcinogenic heterocyclic amines. Enhancement of the activities of their phase II counterparts, such as glutathione S-transferase might have also played a critical role in post-initiation suppression in a study of tongue carcinogenesis. Anti-metastatic effects were moreover detected when bLF was given intragastrically to mice bearing highly metastatic colon carcinoma 26 cells (Co 26Lu), with apparent enhancing influence on local and systemic immunity. Marked increase in the number of cytotoxic T and NK cells in the mucosal layer of the small intestine and peripheral blood cells was thus found, this in turn enhancing the production of Interleukin 18 (IL-18) and caspase-1 in the epithelial cells of the small intestine, with possible consequent induction of interferon (IFN)-gamma positive cells. Furthermore, bLF has been found to exert anti-hepatitis C virus (HCV) activity in a preliminary clinical trial in patients with chronic active hepatitis due to this virus, a main causative factor in hepatocellular carcinoma development in Japanese. More extensive clinical trials are now underway in the National Cancer Center Hospital and other institutes to further explore the preventive potential against colon carcinogenesis.

Inhibition of azoxymethane-induced rat colon carcinogenesis by potassium hydrogen D-glucarate.

While calcium D-glucarate was shown to inhibit chemical carcinogenesis in various animal models, the effect of potassium hydrogen D-glucarate has not been extensively investigated. In the present study, potassium hydrogen D-glucarate markedly inhibited azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. Potassium hydrogen D-glucarate (PHG) or potassium hydrogen carbonate (PHC) were administered to rats in a diet (140 mmol/kg). Continual post-initiation treatment with potassium hydrogen D-glucarate reduced both tumor incidence and multiplicity at sacrifice by ca. 60%, while PHC had no effect. amelioration of overexpression of the betaG gene in rat colon carcinomas was observed using RT-PCR and Northern blot analysis. We hypothesize that previously demonstrated conversion of PHG to D-glucaro-1,4-lactone, a potent inhibitor of beta-glucuronidase (betaG), may be responsible for this effect. The mechanism of PHG inhibition of colon carcinogenesis may also involve suppression of cell proliferation and possibly alterations in cholesterol synthesis or cholesterol metabolism to bile acids. In conclusion, PHG possesses excellent potential as a natural, apparently non-toxic inhibitor to prevent colon cancer.

Possible Mechanisms by Which Pro- and Prebiotics Influence Colon Carcinogenesis and Tumor Growth

Oligofructose and inulin, selective fermentable chicory fructans, have been shown to stimulate the growth of bifidobacteria, which are regarded as beneficial strains in the colon. Studies were designed to evaluate inulin (Raftiline) and oligofructose (Raftilose) for their potential inhibitory properties against the development of colonic aberrant crypt foci (ACF) in rats. ACF are putative preneoplastic lesions from which adenomas and carcinomas may develop in the colon. The results of this study indicate that dietary administration of oligofructose and inulin inhibits the development of ACF in the colon, suggesting the potential colon tumor inhibitory properties of chicory fructans. The degree of ACF inhibition was more pronounced in animals given inulin than in those fed oligofructose. Because these prebiotics selectively stimulate the growth of bifidobacteria, ornithine decarboxylase (ODC) activities, ras-p21 ontoprotein expressions and tumor inhibitory activity of lyophilized cultures of Bifidobacterium longum against chemically induced colon and mammary carcinogenesis and against colonic tumor cell proliferation were examined. Dietary administration of lyophilized cultures of B. longum strongly suppressed colon and mammary tumor development and tumor burden. Inhibition of colon carcinogenesis was associated with a decrease in colonic mucosal cell proliferation and activities of colonic mucosal and tumor ornithine decarboxylase and ras-p21. Human clinical trials are likely to broaden our insight into the importance of the pre- and probiotics in health and disease.

Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene.

Epidemiological studies have suggested a protective effect of lycopene and lycopene‐rich tomatoes against various cancers. Here, the inhibition of colon carcinogenesis by lycopene and tomato juice was investigated. Seven‐week‐old female F344/NSlc rats received an intrarectal dose of 2 mg (experiment I) or 4 mg (experiment II) of N‐methylnitrosourea 3 times a week for 3 weeks, and had free access to one of 4 drinking fluids: plain water (control group), 17 ppm lycopene water solution (Ly group), and diluted tomato juice containing 17 ppm (Tj group) or 3.4 ppm (tj group) lycopene, throughout the experiments. The colon cancer incidence at week 35 was significantly lower in the Tj group, but not in the Ly group, than in the control group: 21% and 33% vs. 54%, in experiment I (24 rats in each group). It was significantly lower in the Tj group than in the tj and control groups, 40% vs. 72% and 84%, in experiment II (25 rats in each group). An appreciable amount of lycopene (0.02 μ/g) was detected in the colon mucosa of rats in the Tj group, but not in the tj group. The results suggest that tomato juice rich in lycopene may have a protective effect against colon carcinogenesis.

Prevention of colon cancer by pre- and probiotics: evidence from laboratory studies

Oligofructose and inulin, selective fermentable chicory fructans, have been shown to stimulate the growth of bifidobacteria which are regarded as beneficial strains in the colon. Studies were designed to evaluate inulin (Raftiline) and oligofructose (Raftilose), for their potential inhibitory properties against aberrant crypt foci (ACF) formation in the colon of rats. ACF are putative preneoplastic lesions from which adenomas and carcinomas may develop. The results of this study demonstrate that dietary administration of oligofructose and inulin inhibits the formation of preneoplastic lesions in the colon suggesting the potential colon tumour inhibitory properties of chicory fructans. Since these prebiotics selectively stimulate the growth of bifidobacteria, tumour inhibitory activity of lyophilized cultures of Bifidobacterium longum (BL) against azoxymethane (AOM)-induced colon carcinogenesis in rats and modulating effect of these cultures on colonic tumour cell proliferation, ornithine decarboxylase (ODC) activity, and ras-p21 oncoprotein expression were investigated. Dietary administration of lyophilized cultures of BL strongly suppressed AOM-induced colon tumour development. Inhibition of colon carcinogenesis was associated with a decrease in colonic mucosal cell proliferation and colonic mucosal and tumour ODC and ras-p21 activities.

COLON CARCINOGENESIS MODELS FOR CHEMOPREVENTION STUDIES

Every animal model has its strengths and weaknesses; however, some of these models have proven useful in evaluating hereditary factors, whereas other models were found to be useful in understanding the relationship between nutritional factors and colon cancer. We believe that the results obtained by these models, both genetic based and chemically induced, will contribute to the understanding of genetic and nutritional factors as they relate to colon carcinogenesis.

Inhibition of Colon Carcinogenesis by Non-nutritive Constituents in Foods.

In addition to mutagens and/ or carcinogens many modulators in carcinogenesis exist in our environment. Some of them are contained in our regular foods and therefore dietary factors play a role in the development of some types of cancers including colon cancer. There are still many unknown constituents and/ or factors in foods that could either enhance or reduce the possibilities for developing cancer. Recent research indicated that in addition to the macro- and micronutrients, many common foods contain nonnutritive components, belonging to different chemical groups, that may protect against certain type of cancer including colon neoplasm. These chemicals are knows as “chemopreventive agents”. The mode of action of most chemopreventive agents is still unknown, although many of them are antioxidants. With increasing the incidence of colon cancer rising certainly, there is an ever increasing need to determine the most effective means to prevent colon cancer and to understand the mechanism(s) underlying successful prevention. Previous studies in our laboratory demonstrated protective effects of several naturally occurring and synthetic compounds against rat colon tumorigenesis. This article will introduce our recent studies in search for the chemopreventive effects of some flavonoids and other naturally occurring products in edible plants on colon carcinogenesis.