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- 주제어 : Azoxymethane (검색결과 59 건)
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랫드에서 azoxymethane으로 유도된 대장 전암병변에 대한 피티산의 방어 효과
허진주,이예은,이기남,남상윤,안병우,윤영원,이범준 한국식품위생안전성학회 2008 한국식품위생안전성학회지 Vol.23 No.3
Phytic acid (PA) (Inositol hexaphosphate, IP6) 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 (1st and 2nd 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 ± 22.3 ACF/colon and 336.6 ± 55.1 AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dosedependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were 124.4 ± 28.5 and 302.7 ± 67.3, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 109 ± 18.1 and 254.8 ± 50.6, respectively (p < 0.01). Especially, 2% PA significantly reduced the number of large ACF ( ≥ 4 AC/ ACF) from 26.8 ± 6.2 ACF/colon to 15 ± 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. Phytic acid (PA) (Inositol hexaphosphate, IP6) 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 (1st and 2nd 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 ± 22.3 ACF/colon and 336.6 ± 55.1 AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dosedependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were 124.4 ± 28.5 and 302.7 ± 67.3, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 109 ± 18.1 and 254.8 ± 50.6, respectively (p < 0.01). Especially, 2% PA significantly reduced the number of large ACF ( ≥ 4 AC/ ACF) from 26.8 ± 6.2 ACF/colon to 15 ± 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.
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American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice
Yu, Chunhao,Wen, Xiao-Dong,Zhang, Zhiyu,Zhang, Chun-Feng,Wu, Xiao-Hui,Martin, Adiba,Du, Wei,He, Tong-Chuan,Wang, Chong-Zhi,Yuan, Chun-Su The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.1
Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.
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American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice
Chunhao Yu,Xiao-Dong Wen,Zhiyu Zhang,Chun-Feng Zhang,Xiao-Hui Wu,Adiba Martin,Wei Du,Tong-Chuan He,Chong-Zhi Wang,Chun-Su Yuan 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.3
Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gutspecific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.
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Saad, Norazalina,Esa, Norhaizan Mohd,Ithnin, Hairuszah Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5
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.
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Suppression of Azoxymethane-Induced Colorectal Tumors in iNOS<SUP>-/-</SUP> C57BL/6J Mice
Mina Choi,Hyun Ye Jo,Beom Seok Han,Dong Deuk Jang,Dae Joong Kim,Sang Yoon Nam,Yun-Bae Kim,Beom Jun Lee,Young Won Yun,Byeongwoo Ahn 한국실험동물학회 2006 Laboratory Animal Research Vol.22 No.2
Nitric oxide (NO) is known to be involved in the pathogenesis of colorectal cancer in both rodents and humans. iNOS is responsible for the over production of NO in a variety of parenchymal cells and macrophages. In the present study, we utilized iNOS gene knockout mice to investigate the role of iNOS on chemical-induced colorectal polyposis. Azoxymethane (AOM) at a dose of 10 ㎎/㎏ body weight was administered to male and female iNOS<SUP>-/-</SUP> or iNOS wt C57BL/6J mice once a week for six weeks. The mice were sacrificed at 24 weeks after initiation of experiment and then examined with the incidence and multiplicities of colorectal polyps. The incidence of colorectal tumors were significantly reduced in iNOS gene knockout mice (22.9%), compared to that of control mice (61.4%). The multiplicity in colorectal polyps in the iNOS knockout mice were 0.37±0.77 (n = 35), being significantly less than wild type mice (1.02 ± 1.15, n = 44). The sizes of the polyps in the iNOS gene knockout mice were also decreased. However, according to histopathological observations, most of the adenocarcinomas from iNOS knockout mice were less differentiated compared to those of wild type mice. From the results, iNOS-mediated NO might have a promotive potential in the early stage, but a suppressive effect in the late stage of colorectal carcinogenesis.
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Waly, Mostafa I.,Ali, Amanat,Guizani, Nejib,Al-Rawahi, Amani S.,Farooq, Sardar A.,Rahman, Mohammad S. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8
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.
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Guizani, Nejib,Waly, Mostafa Ibrahim,Singh, Vandita,Rahman, Mohammad Shafiur Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9
Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.
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He, Xiao-Qiong,Cichello, Simon Angelo,Duan, Jia-Li,Zhou, Jin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6
Azoxymethane (AOM) is a potent genotoxic carcinogen which specifically induces colon cancer. Hyperlipidemia and diabetes have several influences on colon cancer development, with genetic and environmental exposure aspects. Here, we investigated plasma lipid and glucose concentrations in Kunming mice randomized into four groups; control (no AOM or oil exposure), AOM control, AOM + pork oil, and AOM + canola oil. Aberrant crypt foci (ACF), plasma cholesterol, plasma triglyceride, plasma glucose and organ weight were examined 32 weeks after AOM injection. Results revealed that AOM exposure significantly increased ACF number, plasma triglyceride and glucose level. Further, male mice displayed a much higher plasma triglyceride level than female mice in the AOM control group. Dietary fat significantly inhibited AOM-induced hypertriglyceridemia, and canola oil had stronger inhibitory effect than pork oil. AOM-induced hyperglycemia had no sex-difference and was not significantly modified by dietary fat. However, AOM itself not change plasma cholesterol level. AOM significantly increased liver and spleen weight in male mice, but decreased kidney weight in female mice. On the other hand, mice testis weight decreased when fed canola oil. AOM could induce colorectal carcinogenesis, hypertriglyceridemia and hyperglycemia in Kunming mice at the same time, with subsequent studies required to investigate their genome association.
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