• 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.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.

• Journal of Gastric Cancer
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• v.2 no.2
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• pp.73-80
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• 2002

In spite the fact that H. pylori infection might be the causative organisms of acute and chronic gastritis, peptic ulcer diseases and the definition as the class I carcinogen by WHO IARC, still debates exist about the relationship between H. pylori and gastric carcinogenesis. Epidemiological and animal studies demonstrated a link between gastric cancer and chronic infection with H, pylori, but the exact mechanism responsible for the development of gastric cancer in H. pylori-infected patients still remain obscure. In order to declare the clear association, definate evidences like that decrement in the incidence of gastric cancer after the eradication of H. pylori in designated area compared to noneradicated region or the blockade of specific mechanism acting on the carcinogenesis by H. pylori infection. The other way is to identify the upregulating oncogenes or downregulating tumor suppressor genes specifically invovled in H. pylori-associated carcinogenesis. For that, we established the animal models using C57BL/6 mice strain. Already gastric carcinogenesis was developed in Mongolian gerbils infected with H. pylori, but there has been no development of gastric cancer in mice model infected with H. pylori after long-term evaluation. Significant changes such as atrophic gastritis were observed in mice model. However, we could observe the development of mucosal carcinoma in the stomach of transgenic mice featuring the loss of TGF-beta sig naling by the expressions of dominant negative forms of type II receptor specifically in the stomach. Moreover, the incidence of gastric adenocarcinoma was significantly increased in group administered with both MNU and H. pylori infection than MNU alone, signifying that H. pylori promoted the gastric carcinogenesis and there might be host susceptibility genes in H. pylori-associated gastric carcinogenesis. Based on the assumption that chronic, uncontrolled inflammation might predispose to carcinogenesis, there have been several evidences showing chronic atrophic gastritis predisposed to gastric carcinogenesis in H. pylori infection. Although definite outcome of chemoprevention was not drawn after the longterm administration of anti-inflammatory drug in H. pylori infection, the actual incidence of atrophic gastritis and molecular evidence of chemoprevention could be obtained. Selective COX-2 inhibitor was effective in decreasing the development of gastric carcinogenesis provoked by H. pylori infection and carcinogen like in chemoprevention of colon carcinogenesis.

• Journal of Sericultural and Entomological Science
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• v.49 no.2
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• pp.67-70
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• 2007

This study was done for the dietary effect of silk protein, molecular controlled silk sericin and silk fibroin, on colon cancer of animal. The ICR mice were given weekly injections of 1,2-dimethylhydrazine (DMZ) for the initial 10 mg/kg with four weeks, and fed a diets supplemented with 3% (v/v) molecular controlled sericin and fibroin for 6 weeks, respectively. Then, the body weight, efficiency of dietary, typical histologic appearance of animal colon tissue and COX-2 effect were studied, too. Molecular controlled sericin protein are shown more higher dietary effect on animal colon cancer than fibroin supplemental case. The results suggest a potential usefulness of sericin as a chemopreventive for colon carcinogenesis and the development functional food.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4651-4657
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• 2014

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently ($IC_{50}$ of 3mg/mL) in comparison to Gelam honey ($IC_{50}$ of 75mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the $IC_{50}$ of Gelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose-dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.

• Journal of Nutrition and Health
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• v.33 no.7
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• pp.717-724
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• 2000

A number of epidemiological studies has indicated lifestyles including dietary habits are closely related to the development of certain forms of cancer. These findings have led several investigators to identify the ways in which these factors mdulate the risk of cancer. Seaweeds are rich sources of non-digestible polysaccharides which possibly posses physiological functions. In vitro studies showed several components in seaweeds inhibit tumor cell growth and mutagenicity of known food mutagens. On the other hand non-digestible polysaccharides of different food sources negatively affect mineral nutrition by decreasing mineral absorption. The objectives of this study was to investigate the effect of major seaweed intake on azoxymethane(AOM) - induced DNA damage a known cancer initiation step and on apparent absorption of calcium and iron. To accomplish these objectives twenty five ICR mice were divided into five groups and fed one of the following diets for 10 days : control diet d, diet containing 10% water-soluble fraction of seamustard or seatangle diet containing 10% water-insoluble fraction of seamustard or seatangle. AOM was injected 6 hours before sacrifice and N7-methylated guanines from the colonic DNA were quantified using a gas chromatography -mass spectroscopy. Fecal samples were collected on days 4 and 8. Caclium and iron contents of the diets and feces were analyzed using an atomic absorption spectrophotometry to determine the apparent absorption of these minerals. Results are as follows. AOM-induced guanine methylation of colon was decreased in animals fed diets containing water-soluble fractions of seamustard or seatangle compared to those in animals fed control diet although only the seatnagle fed group showed statistically significant effect. Apparent calcium absorption was significantly reduced in animals fed diets containing water-insoluble fractions of seaweeds. Iron absorption was significantly decreased and negatively balanced in animals fed diets containing water-insoluble fractions of both seaweeds, and water-soluble fraction of seatangle. In conclusion, seamustard and seatangle intakes may effectively prevent colon tumorigenesis by reducing a carcinogen-induced DNA damages, and more mechanistic studies on possible role of seaweeds on carcinogenesis are required. Also, adverse effects of seaweed diets cintaming a large amount of polysaccharides on mineral nutrition should be carefully monitored.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7149-7152
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• 2014

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

• Journal of Nutrition and Health
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• v.35 no.5
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• pp.505-511
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• 2002

The study was designed to compare the anti-carcinogenic effect of different level of conjugated linoleic acid (CLA) in 1,2-dimethylhydrazine (DMH)-treated rats by determining biomarkers (apoptosis, cell proliferation, eicosanoids, 1,2-diacylglycerol) and phospholipid fatty acid profile in colonic mucosa. Eighty male Sprague Dawley rats weighing 180-220g were randomly divided into 4 groups depending on the content of CLA, i.e. 0.0% CLA, 0.5% CLA, 1.0% CLA, 1.5% CLA. The experimental diet contained protein 21.6%, carbohydrate 54.6%, and fat 14.5% including CLA mixture at different level by weight. The experimental diet was fed for 14 weeks with the initiation of intramuscular injection of DMH, which was injected twice a week for 6 weeks to give total amount of 180 mg/kg body weight. Regardless of the amount of CLA supplemented to diet, CLA significantly increased the apoptotic index but did not have significant effect on cell proliferation in colonic mucosa. CLA was undetected in colonic mucosal phospholipid of rats fed the 0% CLA diet and increased to 5.9mg/g phospholipid in rats fed the 0.5% diet. The apoptotic index was increased by 251% and the 1,2-DAG content was decreased by 57% in rats fed 0.5% CLA. No further changes in these variables were observed when CLA in the diet was raised to 1.0% or 1.5%. However, dietary CLA decreased mucosal levels of prostaglandin (PG)E$_2$, thromboxane (TX)B$_2$, and arachidonic acid in dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanism probably involving increased apoptosis.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.465-472
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• 2020

Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G₂/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.

• Journal of Nutrition and Health
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• v.35 no.10
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• pp.1038-1044
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• 2002

The study was designed to observe the effect of conjugated linoleic acid (CLA) on tumor incidence, eicosanoid formation and antioxidant enzyme activities in colonic mucosa and the fecal excretion of deoxycholic acid and lithocholic acid in 1,2-dimethylhydrazine (DMH)-treated rats. One hundred twenty male Sprague Dawley rats were divided into 2 groups, BT (beef tallow diet) group and FO (fish oil diet) group, and each group was again subdivided into 2 groups depending on CLA supplementation, i.e.4 groups of BT, BTC, FO, FOC. All rats were fed experimental diet for 30 weeks, which contained 12% (wt/wt) total dietary fat including 1% (wt/wt) CLA, and were intramuscularly injected with DMH for 6 weeks to give total dose of 180 mg/kg body. CLA-supplemented to BT and FO diet reduced tumor incidence, eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. N-3 fatty acids (mainly DHA) of fish oil diet (FO, FOC group) also reduced tumor incidence and significantly reduced eicosanoid (PGE$_2$ and TXA$_2$) level in colonic mucosa. CLA supplementation and n-3 fatty acid significantly increased colonic mucosal level of superoxide dismutase and glutathione peroxidase activities but reduced secondary bile acids (deoxycholic acid and lithocholic acid) excretion in the feces. In conclusion, CLA supplementation and n-3 fatty acid could reduce tumor incidence by reducing eicosanoids and increasing antioxidant enzyme activities in colon and decreasing the excretion of deoxycholic acid and lithocholic acid in the feces. The data might suggest that CLA supplementation and n-3 DHA rich fish oil may modulate colon carcinogenesis.termediate level of endurance exercise training for 6 weeks did not influence concentrations of most of free amino acid in soleus muscle of rats collected at an overnight fasted and rested state. In contrast, isolucine and leucine concentrations in extensor digitorum longus muscle of exercise-trained rats were significantly lower than those for control animals. These results indicate that aerobic energy metabolism had not been efficiently conducted, and thereby the utilization of BCAA for energy substrate was enhanced in fast twitch oxidative glycolytic fibers of extensor digitorum longus muscle of rats followed exercise-training protocol for 6 weeks.