• The Journal of the Convergence on Culture Technology
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• v.5 no.4
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• pp.431-438
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• 2019

The present study was designed to investigate the chemopreventive effects of supercritical heat radish extracts with anti-constipation acitivity in loperamide-treated rats, on 1,2-dimethylhydrazine(DMH)-induced aberrant crypt foci(ACF) in rat colonic mucosa. Supercritical heat radish extracts was administered in the drinking water(3.2 mg/ml) during the initiation (for 12 weeks) or postinitiation phase(for 9 weeks) of DMH-induced carcicogenesis. Supercritical heat radish extracts coupled with DMH for 12 weeks decreased significantly total number of aberrant crypts(pre-neoplastic lesions) and the number of ACF to 35% and 30%, respectively. The number of ACF with more than four aberrant crypts (crypt multiplicity) was significantly reduced in the colon of rats receiving Supercritical heat radish extracts for 12 weeks. In the group receiving Supercritical heat radish extracts after post-initiation for 9 weeks, only the number of ACF with ${\geq}4$ abberant crypts significantly decreased. Supercritical heat radish extracts, given alone for 12 weeks, did not induced the development of ACF. These results indicate that Supercritical heat radish extracts possess chemopreventive effects on chemically induced rat colon carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1929-1933
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• 2012

Oxidative stress has been proposed to be involved in colorectal cancer development. Many dark pigments of plants have potent oxidative stress preventive properties. In this study, unpolished Thai rice was assessed for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Red strain unpolished Thai rice was also administered to rats exposed to azoxymethane (AOM) for induction of aberrant crypt foci (ACF). Serum malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) were investigated for cellular oxidative stress and serum antioxidants, respectively. Red pigment unpolished Thai rice demonstrated high antioxidant activity and was found to significantly and dose dependently decrease the total density and crypt multiplicity of ACF. Consumption of Thai rice further resulted in high serum antioxidant activity and low MDA cellular oxidative stress. Interestingly, the density of ACF was strongly related to MDA at r = 0.964, while it was inversely related with FRAP antioxidants (r = -0.915, p < 0.001). The results of this study suggest that the consumption of red strain of unpolished Thai rice may exert potentially beneficial effects on colorectal cancer through decrease in the level of oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3551-3558
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• 2016

Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout the world, with chronic inflammation and diet as major causes in its development. Chemopreventive effects of natural dietary products have been the focus of studies for prevention over the past decade. This study was conducted to determine the effects of unpolished Thai rice during precancerous stage through the involvement of ${\beta}$-catenin, cyclooxygenase-2 (COX-2) expression and inflammatory cytokines focusing on azoxymethane (AOM)-induced aberrant crypt foci (ACF)-related to CRC. Male Sprague Dawley rats received two injections of AOM (15 mg/kg body weight) at weeks 4 and 5 while rats were treated with 20% or 70% unpolished Thai rice. The rats were sacrificed at week 38 and the colons removed for aberrant crypt foci (ACF) identification. Histopathologic changes, immunohistochemical analysis of ${\beta}$-catenin and COX-2 expression, and cytokine expression of proinflammatory and anti-inflammatory markers were determined. The administration of unpolished Thai rice significantly and dose dependently decreased the total number of ACF and the percentages of ACF with high-grade dysplasia. Interestingly, unpolished Thai rice suppressed the expression of ${\beta}$-catenin and COX-2. In addition, it also altered proinflammatory (IL-6 and IFN-${\gamma}$) and anti-inflammatory (IL- 10) markers. The results suggested that unpolished Thai rice may provide a promising dietary intake for prevention during precancerous stage of CRC development, through the involvement of ${\beta}$-catenin and COX-2 expression, and also modulate inflammatory cytokines-related to CRC.

• Nutritional Sciences
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• v.8 no.4
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• pp.219-225
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• 2005

This study examined the effect of viable bifidobacteria and non-digestible carbohydrates on the cecal pH, colonic neoplastic lesion (aberrant crypt) and proliferating cell nuclear antigen (PCNA) labeling index in carcinogen-treated mts. Animals received s.c. injection of dimethylhydrazine (DMH) (15 mg/kg body weight) twice 3 days apart. Three days after the second carcinogen administration, the treatments were begun. 1he treatments were basal diet (AIN-76) with skim milk (Basal/skim), or the following diets with daily gavage of $10^8$ bifidobacteria: basal (Basal/bifido), $2\%$ fructo-oligosaccharide (FOS/bifido), $2\%$ soybean oligosaccharide (SBO/bifido), $2\%$ wheat bran oligosaccharide (WBO/bifido) and $8.4\%$ wheat bran (WB/bifido). After 4 weeks of treatment, cecal pH was measured using a pH probe. The number of aberrant crypt (AC), aberrant crypt foci (ACF) and crypt multiplicity were enumerated and colonic PCNA labeling index was determined using immunohistochemistry. Cecal pH was significantly reduced in SBO/bifido and FOS/bifido groups compared to control group. However, there were no significant differences in either number of AC or rates of cell proliferation as shown by PCNA labeling index among the groups, although mts fed FOS/bifido reduced the numbers of ACF compared to Basal/skim group. The SBO/bifido group did not reduce the number of ACF or PCNA labeling index. Also, other oligosaccharides did not reduce the risk of colon cancer compared to control group. The concomitant reduction of cecal pH and number of ACF suggest that the combination of bifidobacteria and FOS may reduce the risk of colon cancer.

• Toxicological Research
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• v.23 no.4
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• pp.321-330
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• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• Biomedical Science Letters
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• v.16 no.4
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• pp.381-385
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• 2010

Indole-3-carbinol (I3C), one of naturally occurring main components in cauliflower vegetables, is supposed to have a chemopreventive potential in experimental animals and humans. This study was investigated to examine chemopreventive effect of I3C on colon carcinogenesis induced by azoxymethane (AOM) using C57BL/6J mice. Mice were divided into three groups (10 or 9 mice/group). All mice were subcutaneously injected with AOM (5 mg/kg body weight, four times at weekly interval). After AOM treatment, animals of group 1 were fed by AIN-76A pellets as a basal diet. Animals of groups 2 and 3 were given I3C containing diets (100 and 300 ppm in diets, respectively) for 6 weeks until sacrifice. All mice were sacrificed at week 10 and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Total numbers of ACF/colon in group 2 ($10.1{\pm}5.1$) or group 3 ($10.6{\pm}5.3$) were decreased compared to the values of group 1 ($14.4{\pm}10.2$). Among numbers of ACF formation, 5, 7, 8 and 10 ACF in group 2 and 3 were greatly different those of group 1. Total numbers of aberrant crypts (AC)/colon of group 2 ($20.1{\pm}10.1$) or group 3 ($22.0{\pm}10.9$) were decreased compared to the value of group 1 ($33.7{\pm}24.7$). Taken together, it suggests that I3C treatment may retard mouse colon carcinogenesis even after administration of AOM.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3881-3885
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• 2015

Obesity markedly increases the risk of colorectal cancer. Recently, the preventive effects of edible mushrooms on triglyceride elevation and visceral fat accumulation have been reported. Here, the effects of Pleurotus eryngii (Eringi) and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant crypt foci (ACF; precancerous lesions) in the colorectums of mice fed a high-fat diet were examined. Eringi (ER) and Bunashimeji (BU) mushroom powder samples were used. Six-week-old male C57BL/6J mice received an intraperitoneal injection of AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6 weeks after the start of the experiment. After the initiation of the experiment, they received a normal diet (ND), high-fat diet (HFD), HFD + ER (1 or 5% of diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights were significantly lower in the 5% ER and BU groups than in the HFD group. Liver triglyceride levels were also significantly lower in the 5% ER and BU groups. Total liver cholesterol levels were significantly lower in the 5% ER group. The numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER and BU groups. Measurement of the cell proliferation marker Ki-67 labeling index in the colonic mucosa demonstrated more significant suppression in both ER and BU groups than in the HFD group. These results suggest that the simultaneous intake of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice.

• Korean Journal of Veterinary Research
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• v.48 no.3
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• pp.337-345
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• 2008

There are accumulating evidences that high levels of dietary iron may play a role in colon carcinogenesis. Elevated iron status has been associated with oxidative stress. Phytic acid (PA) functions as an antioxidant by chelating divalent cations and prevents formation of reactive oxygen species responsible for cell injury and carcinogenesis. The protective effect of PA was investigated on formation of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in iron-overloaded male F344 rats. After acclimation with AIN-93G purified diet (35 ppm Fe, normal control diet) for one week, animals were fed iron-overloaded diet (350 ppm Fe) and PA (0.5% or 2% PA in water) for 8 weeks. Animals received two (1st and 2nd week) injections of AOM (15 mg/kg b.w.) to induce colonic ACF. The colonic mucosa was examined for the total numbers of aberrant crypt (AC) and ACF after staining with methylene blue. The blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. Iron-overloaded diet increased the concentration of iron in liver of the rats. But iron-related parameters in blood were not changed among experimental groups. The numbers of ACF per colon and AC per colon were $178.8{\pm}33.2$ and $448.4{\pm}110.2$ in the iron-overloaded F344 rats. The total AC was significantly increased, compared with normal-diet AOM control group (p < 0.05). The treatments of PA at the dose of 0.5% slightly decreased the number of ACF and AC per colon to $153.6{\pm}29.5$ and $396.3{\pm}107.5$. However, there were no significant differences in the total numbers of ACF and AC between the AOM control group and PA (0.5% or 2%)-treated groups. These results suggest that PA may not affect the formation of ACF or AC induced by AOM in ironoverloaded F344 rats.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2827-2832
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• 2015

Oxidative stress is associated with colon carcinogenesis including aberrant crypt foci (ACF) formation and it plays an important role in pathophysiological changes in cancer cells. The aims of this study were to investigate the effects of dietary unpolished Thai rice (UTR) on ACF formation and dysplastic progression in azoxymethane (AOM)-treated rats. Anti-cancer efficacy of UTR regarding apoptotic induction and oxidative redox status in human colon cancer (CaCo-2) cells was also investigated. Rats given 20% and 70% of UTR in the diet showed significantly and dose-dependently decreased total number of ACF. UTR treatment also was strongly associated with the low percentage of dysplastic progression and mucin depletion. In addition, we found that UTR significantly induced cancer cell apoptosis, increased cellular oxidants, and decreased the level of GSH/GSSG ratio in CaCo-2 cells. Our study suggests that UTR supplementation may be a useful strategy for CRC prevention with the inhibition of precancerous progression, with induction of cancer cell apoptosis through redox alteration.

• Preventive Nutrition and Food Science
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• v.13 no.3
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• pp.157-165
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• 2008

Cancer-preventive effects of ethanol extract of elm tree root (EEE) were investigated. In the in vitro cytotoxicity assay, colon cancer cells were incubated with a chloroform fraction of EEE (CF-EEE). CF-EEE significantly inhibited the proliferation of cells and induced apoptotic cell death in a dose-dependent manner. For the assessment of chemopreventive efficacy in vivo, male F344 rats were fed with EEE (0.5 or 1%) in diet for 8 weeks, and were subcutaneously injected with 1,2-dimethylhydrazine (DMH) to induce colonic aberrant crypt foci (ACF). EEE (0.5 and 1%) significantly decreased both the numbers of AC (1191.1/colon) and ACF (529.3/colon) induced by DMH. In addition, in the Western blot analysis on the colonic mucosa, administration of EEE triggered expression of caspase-3, a key factor of an apoptotic cascade. These results suggest that extract of elm tree root may have potential chemopreventive principles that lead to apoptosis of cancer cells, and thereby suppress colorectal carcinogenesis during the initiation stage.