• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.683-687
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• 2015

Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4067-4073
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• 2012

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the $PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

• 한국식품위생안전성학회지
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• 제23권3호
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• pp.264-270
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• 2008

대장암은 국민경제 수준의 향상과 식생활의 서구화에 따라 급격하게 증가하여, 등록환자 기준으로 2005년 현재 위암에 이어 두 번째로 많은 상태이다. 특히 육류에 많이 함유된 철분 및 지방의 과다섭취가 주요원인으로 여겨지고 있다. Phytic acid(PA) (Inositol hexaphosphate, IP6)는 식물의 박류, 콩류 등에 약 0.1-5% 농도로 존재하며, 포유류의 세포에서도 존재한다. PA는 금속이온과 결합하는 성질을 갖고 있어서, hydroxyl radical과 같은 활성산소종의 형성을 억제하여 항산화 작용을 나타낸다. 본 연구에서는 PA가 대장암 발생의 전암병변인 aberrant crypt faci(ACF) 의 발생을 억제하는지를 조사하고자 수컷 F344 랫드를 사용하였다. Azoxymethane(AOM)을 실험시작 1주 및 2번째 주에 투여함으로 ACF를 유발하였고, 실험기간은 8주로서 AIN-93G 사료급여와 동시에 음수로서 0.5%와 2% PA를 급여하였다. 부검 후, 혈액검사와 대장암 발생의 초기단계인 ACF를 측정하였다. 결과로서 AOM 투여 대조군과 비교해 볼 때 PA의 농도가 증가함에 따라 ACF와 aberrant crypt(AC)의 수가 감소하였고, 2% PA는 유의적으로 ACF와 AC의 수를 감소시켰으며, 더욱이 4개 이상 AC를 갖는 ACF의 수를 유의적으로 감소시켰다. 또한 혈액 생화학적 수치에서 어느 정도 유의적 변화가 나타났지만 정상범위내에서의 변화로서 인정될 수 있을 것이다. 본 실험에서 이러한 결과는 phytic acid가 대장암 발생과정에 전암병변의 형성을 억제함으로서 최종 대장암발생에 억제효과를 나타낼 수 있을 것이라 사료된다.

• 한국식품위생안전성학회지
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• 제25권3호
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• pp.269-277
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• 2010

본 연구에서는 azoxymethane (AOM)과 dextran sodium sulfate (DSS)로 유도된 대장 발암과정에 대한 셀레늄의 방어 효과를 조사하였다. 셀레늄 결핍(0.02 ppm Se), 정상(0.1 ppm Se), 과다(0.5 ppm Se)사료를 12주간 식이로 급여하여 혈액검사와 대장암 발생의 초기단계인 aberrant crypt foci (ACF)수를 측정했으며, 암 발생율을 조사하였다. ICP-AES를 사용하여 간의 셀레늄 농도를 측정하였으며, 또한 셀레늄포함 항산화효소인 glutathione peroxidase (GPx) 활성을 알아보았다. 또한 TUNEL assay와 PCNA, $\beta$-catenin에 대한 면역조직 염색을 수행하였다. ACF 수 및 종양 발생률에 있어서, 셀레늄과다사료를 급여한 군이 정상셀레늄사료를 급여한 군보다 낮았으며, 셀레늄결핍사료를 급여한 군은 오히려 ACF 수 및 종양 발생률이 높았다. GPx 활성은 셀레늄의 섭취가 과다한 군에서 높게 나타났으며, 이 때, TUNEL에서 apoptotic positive cell이 증가하는 것을 확인했다. 또한 셀레늄의 섭취가 과다한 군에서 PCNA와 $\beta$-catenin의 발현이 감소됨을 볼 수 있었다. 본 마우스 모델실험에서 셀레늄은 여러 기전에 의해 대장암 발생을 억제할 수 있을 것으로 사료된다.

• Preventive Nutrition and Food Science
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• 제19권2호
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• pp.82-88
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• 2014

Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental folk medicine because of its nutritional fortification, tonic, anti-diarrheal, anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species (ROS), which are known to be implicated in a range of diseases, may be important progenitors of carcinogenesis. The aim of this study was to investigate the modulatory effect of yam on antioxidant status and inflammatory conditions during azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme activities, colonic mucosal antioxidant enzyme gene expression, and colonic mucosal inflammatory mediator gene expression. The feeding of yam prior to carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam-administered rats, erythrocyte levels of glutathione, glutathione peroxidase (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet. These results suggest that yam could be very useful for the prevention of colon cancer, as they enhance the antioxidant defense system and modulate inflammatory mediators.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6225-6229
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• 2015

Faecal pH and cholate are two important factors that can affect colon tumorigenesis, and can be modified by diet. In this study, the effects of two Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on the pH and the cholic acid content in feces, in addition to colon tumorigenesis, were studied in mice. Kunming mice were randomized into various groups; negative control group (NCG), azoxymethane control group (ACG), pork oil group (POG), and canola oil Ggroup (COG). Mice in the ACG were fed a basic rodent chow; mice in POG and COG were given 10% cooking oil rodent chow with the respective oil type. All mice were given four weekly AOM (azoxymethane) i.p. injections (10mg/kg). The pH and cholic acid of the feces were examined every two weeks. Colon tumors, aberrant crypt foci and organ weights were examined 32 weeks following the final AOM injection. The results showed that canola oil significantly decreased faecal pH in female mice (P<0.05), but had no influence on feces pH in male mice (P>0.05). Pork oil significantly increased the feces pH in both male and female mice (P<0.05). No significant change was found in feces cholic acid content when mice were fed 10% pork oil or canola oil compared with the ACG. Although Kunming mice were not susceptible to AOM-induced tumorigenesis in terms of colon tumor incidence, pork oil significantly increased the ACF number in male mice. Canola oil showed no influence on ACF in either male or female mice. Our results indicate that cooking oil effects faecal pH, but does not affect the faecal cholic acid content and thus AOM-induced colon neoplastic ACF is modified by dietary fat.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• 대한수의학회지
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• 제52권2호
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.368-370
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• 1999

The protective role of Bifidobacterium spp. (B. breve K-110, B. breve K-111, and B. infantis K-525) isolated from the fecal samples of healthy Koreans was investigated on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci(ACF) formation in mouse colon. In mice fed normal diet with DMH treatment, an average of 68.5 ACF/colon was formed, whereas in mice administered with B. breve K-110, B. breve K-111, and B. infantis K-525, the numbers of DMH-induced ACF decreased to 7.2, 10.9, and 6.6 ACF/ colon, respectively. The mean number of crypts/focus was not significantly altered. Fecal harmful enzymes, such as β-glucuronidase, tryptophanase, and urease, were effectively inhibited during the administration of these bifidobacteria to mice. These results suggest that bifidobacteria could prevent colon cancer.

• Food Science and Biotechnology
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• 제15권6호
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• pp.980-985
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• 2006

The goal of this study was to investigate the effects of a newly developed functional food containing Bacillus polyfermenticus (BP) and other physiologically active materials on the antioxidant system and the process of colon carcinogenesis in male F344 rats. Following a one-week adaptation period, the rats were divided into 3 groups and fed either a high-fat, low-fiber diet (control and DMH groups), or a high-fat, low-fiber diet supplemented with B. polyfermenticus ($3.1{\times}10^8\;CFU/day$) and other physiologically active materials (chitosan, chicory, ${\alpha}$-tocopherol, and flavonoids) (DMH+BP group). One week after the initiation of the diets, 2 groups of rats were subjected to six weeks of treatment with 1,2-dimethylhydrazine (DMH, 180 mg/kg BW, s.c.). The dietary treatments remained consistent throughout the entire experimental period. Nine weeks after the initial DMH injection, the rats supplemented with B. polyfermenticus had significantly lower numbers of aberrant crypt foci than those in the DMH group. Injections with DMH resulted in significantly higher leukocytic DNA damage and plasma lipid peroxidation levels, as well as in a lower plasma total antioxidant potential. These effects were reversed following supplementation with B. polyfermenticus and other physiological materials. Our results indicate that a functional food containing B. polyfermenticus exerts a protective effect on the antioxidant system and on the process of colon carcinogenesis, thereby suppressing the development of preneoplastic lesions.