• Korean Journal of Veterinary Research
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• v.52 no.2
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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.

• Polymer(Korea)
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• v.35 no.5
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• pp.483-487
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• 2011

For the preparation of effective non-vascular drug eluting stent (DES), pullulan acetate (PA) was investigated as a coating material for polytetrafluorethylene (PTFE)-covered stent. PA was coated on PTFE-covered stent (PTFE-stent) by dip coating technique, and then its surface morphology, drug release behavior and cellular toxicity were tested. Field emission-scanning electron microscopy (FE-SEM) result indicated that its surface was smoother after PA coating without any cracking. The sustained release behavior of paclitaxel from PA-coated PTFE membrane was observed for 80 days. Also, the biological stability of paclitaxel in the membrane was confirmed by annexin V binding assays. Furthermore, the antitumor activity was demonstrated by an in vivo test against CT-26 murine colorectal tumors. From the results, we concluded that PA was expected as a useful coating material to design an effective non-vascular DES.

• 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.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.270-280
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• 1998

Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

• Journal of the Korean Data and Information Science Society
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• v.27 no.5
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• pp.1169-1182
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• 2016

Cancer is a typical cause of death in Korea that becomes a major issue in health care. According to Cause of Death Statistics (2014) by National Statistical Office, SMRs (standardized mortality rates) in Busan were counted as the highest among all cities. In this paper, we used data of Busan Regional Cancer Center to estimate the extent of the cancer incidence rate and cancer mortality rate. The data are considered in small areas of administrative units such as Gu/Dong from years 2003 to 2009. All cancer including four major cancers (stomach cancer, colorectal cancer, lung cancer, liver cancer) have been analyzed. We carried out model selection and parameter estimation using spatial multi-level model incorporating a spatial correlation. For the spatial effects, CAR (conditional autoregressive model) has been assumed.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.288-297
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• 2018

Background: The incidence of colorectal cancer (CRC) is increasing, with metastasis of newly diagnosed CRC reported in a large proportion of patients. However, the effect of Korean Red Ginseng extracts (KRGE) on epithelial to mesenchymal transition (EMT) in CRC is unknown. Therefore, we examined the mechanisms by which KRGE regulates EMT of CRC in hypoxic conditions. Methods: Human CRC cell lines HT29 and HCT116 were incubated under hypoxic (1% oxygen) and normoxic (21% oxygen) conditions. Western blot analysis and real-time PCR were used to evaluate the expression of EMT markers in the presence of KRGE. Furthermore, we performed scratched wound healing, transwell migration, and invasion assays to monitor whether KRGE affects migratory and invasive abilities of CRC cells under hypoxic conditions. Results: KRGE-treated HT29 and HCT116 cells displayed attenuated vascular endothelial growth factor (VEGF) mRNA levels and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) protein expression under hypoxic conditions. KRGE repressed Snail, Slug, and Twist mRNA expression and integrin ${\alpha}V{\beta}6$ protein levels. Furthermore, hypoxia-repressed E-cadherin was restored in KRGE-treated cells; KRGE blocked the invasion and migration of colon cancer cells by repressing $NF-{\kappa}B$ and ERK1/2 pathways in hypoxia. Conclusions: KRGE inhibits hypoxia-induced EMT by repressing $NF-{\kappa}B$ and ERK1/2 pathways in colon cancer cells.

• YAKHAK HOEJI
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• v.53 no.4
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• pp.184-188
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• 2009

Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.

• Korean Journal of Plant Resources
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• v.28 no.6
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• pp.682-689
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• 2015

Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme and aldose reductase. Recently, our group found that branch extracts of A. distichum (EAFAD-B) induce apoptosis through ATF3 activation in human colon cancer cells. However, anti-cancer reagents exert their activity through the regulation of various molecular targets. Therefore, the elucidation of potential mechanisms of EAFAD-B for anti-cancer activity may be necessary. To elucidate the potential mechanism of EAFAD-B for anti-cancer activity, we evaluated the regulation of cyclin D1 in human colon cancer cells. EAFAD-B decreased cellular accumulation of cyclin D1 protein. However, cyclin D1 mRNA was not changed by EAFAD-B. Inhibition of proteasomal degradation by MG132 attenuated EAFAD-B-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with EAFAD-B. In addition, EAFAD-B induced cyclin D1 phosphorylation at threonine-286 and the point mutation of threonine-286 to alanine attenuated EAFAD-B-mediated cyclin D1 proteasomal degradation. Inhibitions of both ERK1/2 by PD98059 and NF-κB by a selective inhibitor, BAY 11-7082 suppressed cyclin D1 downregulation by EAFAD-B. From these results, we suggest that EAFAD-B-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2-dependent NF-κB activation. The current study provides new mechanistic link between EAFAD-B and anti-cancer activity in human colon cancer cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.5
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• pp.364-371
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• 2002

Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.

• YAKHAK HOEJI
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• v.49 no.1
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• pp.38-43
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• 2005

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.