• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4051-4055
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• 2012

Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3473-3477
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• 2015

Plants and their by-products offer a diverse mixture of chemical constituents like natural antioxidants. Date-pits are rich in phenolic compounds that have antioxidant potential. The main objective of this study was to investigate the protective effect of a date-pit extract (DPE) against AOM-induced colonic carcinogenicity and oxidative stress. Thirty-two weanling male Sprauge-Dawley rats were randomly divided into four groups (eight rats in each group). All rats were fed basic diet and water ad libitum, and randomly distributed per treatment groups as follows: negative controls injected with normal saline once a week for two weeks, a cancer group injected intra-peritoneally with azoxymethane (15mg/kg body weight) for two consecutive weeks, and DPE treated groups receiving the extract via the oral route (1.5ml/day) for the entire experiment in the presence or absence of AOM injection. Results showed that DPE contained phytonutrients that were capable of inhibiting chemically-induced oxidative stress in the rat colonic cells. In those animals that consumed DPE, a protective effect was observed against AOM-induced oxidative stress in rat colonic cells as evident by a significant decrease in MDA and oxidized DCF formation in AOM injected and DPE fed groups. It is concluded that DPE has potential antioxidant and anticarcinogenic properties.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3093-3099
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• 2013

Background: Phytic acid (PA) is a polyphosphorylated carbohydrate that can be found in high amounts in most cereals, legumes, nut oil, seeds and soy beans. It has been suggested to play a significant role in inhibition of colorectal cancer. This study was conducted to investigate expression changes of ${\beta}$-catenin and cyclooxygenase-2 (COX-2) and cell proliferation in the adenoma-carcinoma sequence after treatment with rice bran PA by immunocytochemistry. Materials and Methods: Seventy-two male Sprague-Dawley rats were divided into 6 equal groups with 12 rats in each group. For cancer induction two intraperitoneal injections of azoxymethane (AOM) were given at 15 mg/kg bodyweight over a 2-weeks period. During the post initiation phase, two different concentrations of PA, 0.2% (w/v) and 0.5% (w/v) were administered in the diet. Results: Results of ${\beta}$-catenin, COX-2 expressions and cell proliferation of Ki-67 showed a significant contribution in colonic cancer progression. For ${\beta}$-catenin and COX-2 expression, there was a significant difference between groups at p<0.05. With Ki-67, there was a statistically significant lowering the proliferating index as compared to AOM alone (p<0.05). A significant positive correlation (p=0.01) was noted between COX-2 expression and proliferation. Total ${\beta}$-catenin also demonstrated a significant positive linear relationship with total COX-2 (p=0.044). Conclusions: This study indicated potential value of PA extracted from rice bran in reducing colonic cancer risk in rats.

• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.29-34
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• 2001

This study was conducted to assess the chemopreventive effects of chitosan in a rat colon carcinogenesis induced by azoxymethane (AOM). Ninety, 5-week-old, male F344 rats were divided into three groups. The animals in group 1 received subcutaneous injections of 15mg/kg AOM three times for two weeks, then were placed on powdered basal diet containing 2% chitosan for 37 weeks from weeks 3 to 40. The animals in group 2 were given AOM alone. The animals in group 3 were given 2% chitosan without prior carcinogen treatment. All animals were sacrificed at week 12 for quantitative analysis of aberrant crypt foci (ACF) and at week 40 fur analysis of tumor induction. Total numbers of ACF and AC per colon of group 1 were not significantly different from those of group 2. Tumor incidences and multiplicities of small intestine in the group 1 were significantly decreased compared with those of the group 2 (P<0.05). According to pathological diagnoses, adenocarcinoma incidence and multiplicity in the small and large intestine in the group 1 were significantly decreased compared with those of the group 2 (p<0.05). No toxic effects were observed in animals given chitosan in terms of body weights, and liver or kidney histology. These results indicate that chitosan may have a potential as chemopreventive agents of colon carcinogenesis during the postinitiation stage.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6851-6856
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• 2013

In the present report we determined the protective capacity of grapefruit juice (GJ) against molecular and cellular damage in azoxymethane (AOM) treated mice. Animals were daily administered GJ orally (0.8, 4.1, and 8.2 ${\mu}l/g$) for seven weeks, as well as intraperitoneally (ip) injected with AOM twice (weeks 2 and 3 of the assay). Control groups administered with water, with the high dose of GJ, and with AOM injected in weeks 2 and 3 were also included. The results showed a significant, dose-dependent protection of GJ on the number of colon aberrant crypts (AC) induced by AOM. The highest inhibitory effect was reached with the highest tested dose of GJ, decreasing ACF by 51% and 43% at weeks 4 and 7 of the assay. Regarding protein and lipid oxidation we also found a dose-dependent decrease caused with GJ in comparison with the increased levels produced by AOM. Therefore, our results established chemopreventive potential for GJ, and suggested effects related to its antioxidant capacity. Finally, we found that the tested agents induced neither micronuclei increase nor alteration in bone marrow cytotoxicity.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.281-289
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• 2017

BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been attributed to higher intake of fat and protein. However, reports on the relationship between protein intake and CRC are inconsistent, possibly due to the complexity of diet composition. In this study, we addressed a question whether alteration of protein intake is independently associated with colonic inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were randomly divided into 4 experimental groups: 20% protein (control, 20P, 20% casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30% casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis. RESULTS: As the protein content of the diet increased, clinical signs of colitis including loss of body weight, rectal bleeding, change in stool consistency, and shortening of the colon were worsened. This was associated with a significant decrease in the survival rate of the mice, an increase in proinflammatory protein expression in the colon, and an increase in mucosal cell proliferation. Further, colon tumor multiplicity was dramatically increased in the 30P (318%) and 50P (438%) groups compared with the control (20P) group. CONCLUSIONS: These results suggest that a high protein diet stimulates colon tumor formation by increasing colonic inflammation and proliferation.

• Journal of Food Hygiene and Safety
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• v.23 no.3
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• pp.264-270
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• 2008

Phytic acid(PA) (Inositol hexaphosphate, $IP_6$) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA(0.5% or 2% PA in water) for 8 weeks. The animals received two ($1^{st}\;and\;2^{nd}$ week) injections of azoxymethane(AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci(ACF). After sacrifice, the total numbers of aberrant crypts(AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of $142.3{\pm}22.3$ ACF/colon and $336.6{\pm}55.1$ AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were $124.4{\pm}28.5\;and\;302.7{\pm}67.3$, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to $109{\pm}18.1\;and\;254.8{\pm}50.6$, respectively(p<0.01). Especially, 2% PA significantly reduced the number of large ACF(${\geq}4$ AC/ACF) from $26.8{\pm}6.2$ ACF/colon to $15{\pm}6.7$ ACF/colon(p<0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

• Journal of Microbiology
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• v.38 no.3
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• pp.169-175
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• 2000

Epidemiological and experimental studies provide evidences that diet and intestinal microflora play an important role in colon carcinogenesis. In recent years, it has been suggested that lactic acid bacteria (LAB) used to ferment dairy products have an inhibitory effect on the colon cancer. This study was designed to determine the effect of Bifidobacterium longum HY8001 (Bif) and Lactobacillus acidophilus HY2104(Lac) of Korean origin on azoxymethane (AOM)-induced colonic preneoplastic lesions such as aberrant crypt foci(ACF) formation and cecal pH. At five weeks of age, Spraque-Dawley rats were divided at random into four (AOM alone, Bif, ,Lac, and Bif+Lac) groups. Animals were weighed weekly and oral administration of LAB cultures were performed daily until the termination of the study. Two weeks later, all animals were given a subcutaneous injection of AOM dissolved in normal saline at a dose of 15 mg/kg of body weight once per week for 2 weeks. All rats were necropsied 7 weeks after the last AOM injection , and the ACF were visualize under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons. The total number of aberrant crypt in Bif, Lac, and Bif+Lac groups were significantly lower than that of the AOM alone group and the percentage of inhibitions weas 35.0, 45.6%, respectively. Significant inhibition (p<0.001) in the total number of ACF was also observed in LAB treated groups (Bif , Lac, and Bif+Lac group by 3003, 38.6, and 41.2%, respectively). Furthermore, cecal pH appeared to significantly decrease by LAB administration. The results of present study provide some evidences for potential colon tumor-inhibitory properties of lactic cultures and fermented dairy products.

• Nutritional Sciences
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• v.2 no.2
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• pp.71-75
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• 1999

Epidemiologic studies consistently demonstrate an inverse relationship between risk for colon canter and consumption of fruits and vegetables. Wheat bran, flax and soy contain dietary fiber and phytochemicals, such as lignans and isoflavones, that may inhibit colon carcinogenesis. Orange juice contains hesperidin, a flavanone glucoside that protects against colon carcinogenesis. This study determined if feeding orange juice, wheat bran, soy and flaxseed (combined diet) would inhibit azoxymethane (AOM) induced colon cancer. Cancer was initiated in male Fisher 344 rats by injecting 15 mg AOM/kg of weight at 22 and 29 days of age. One week after the second AOM injection, rats (N = 30) in the combined diet group received dry diet containing wheat bran (4%), soy with ethanol soluble phytochemirals(13%) and flaxseed (8%) and orange juice replaced drinking water. The control group remained on the control diet and received distilled water to drink. The rats were killed 28 weeks later, and colon tissues and tumors were removed for histologic analysis. Feeding the combined diet significantly reduced tumor incidence (p < 0.05), however tumor multiplicity was not changed (p > 0.05, 0.9 tumors/rat fed the combined diet vs 1.2 for controls). Also, tumor burden was only marginally reduced in rats fed the combined diet vs control rats (65 vs 210 mg of tumor/rats, respectively). The reduction in tumor incidence was associated with a decreased labeling index and proliferation zone in normal appearing colon mucosa. Therefore, this study shows that phytochemicals in wheat bran, soy, flax and orange juice reduce colon carcinogenesis, presumably by decreasing cell proliferation and enhancing cell differentiation.

• Nutritional Sciences
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• v.7 no.2
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• pp.76-82
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• 2004

Pine needles are known as a traditional medicine and their ingestion has been shown to be beneficial to human beings. Following induction of the neoplastic process in rats by azoxymethane (AOM), we determined the effects of pine needle supplementation on colon carcinogenesis and on antioxidant systems in the blood and liver. Five week old male Fisher 344 rats were injected with AOM (15 mg/kg) once a week for two weeks. After the second injection, 18 rats were randomly assigned into two groups and were fed a casein-based high-fat diet (120 g fat and 1 g cholesterol/kg diet) with or without pine needle powder (10%w/w). After 6 weeks, rats receiving pine needle powder showed a 40% lower incidence of the number of colonic preneoplastic lesions (aberrant crypts) and a 52% lower incidence of aberrant crypt foci (p<0.01). A significantly elevated level of erythrocyte catalase activity was observed in the pine needle supplemented group (17.4$\pm$1.1 vs. 24.5$\pm$1.5, p<0.01). Pine needle supplementation also increased liver glutathione peroxidase activity (7.5$\pm$0.6 vs. 14.6$\pm$0.6, p<0.01). Other antioxidant parameters such as erythrocyte glutathione peroxidase, liver catalase activity, and plasma total antioxidant potential (TRAP), showed no statistical differences between the two groups. Our data demonstrate that pine needle supplementation improves the antioxidant system and suppresses the formation of colonic preneoplastic lesions in AOM-treated rats. This result provides additional insights into the chemo-preventative properties of pine needles.