• Nutrition Research and Practice
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• v.6 no.5
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• pp.396-404
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• 2012

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane ${\beta}$-catenin but decreased nuclear ${\beta}$-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in $Apc^{Min/+}$ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were ${\geq}$ 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of ${\beta}$-catenin (expressed as nuclear positivity), but increased plasma membrane staining of ${\beta}$-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and $Apc^{Min/+}$ mice. The decreased ${\beta}$-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.151-161
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• 2001

Background: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost. In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. Method: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. Results: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. Conclusion: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.

• 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.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.83-88
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• 2004

Galectin family, endogenous ${\beta}$-galactoside-binding animal lectins, is known for the role in cell differentiation, morphogenesis, apoptosis and tumorigenesis. Galectin-3, one of family member, has been studied for its role in cell differentiation and tumor metastasis, and for its expression on epithelial cells of colon and mast cells but not in brain. Several reports, however, suggest its expression in brain including as a prion binding protein. In this report we explored possibility of galectin-3 expression in brain tissue. With Western blot and RT-PCR with rat brain tissues, we could detect galectin-3 that was not shown by conventional immunohistochemistry. Our results indicated galectin-3 was expressed in brain, and substantiate the previous report on galecin-3 as a prion-related protein in brain.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.49-56
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• 2011

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

• BMB Reports
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• v.51 no.3
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.

• Journal of Life Science
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• v.21 no.2
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• pp.194-201
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• 2011

Caudal-related homeodomain proteins play critical roles in intestine development and maintenance from Drosophila to humans. The loss or reduction of CDX1 and CDX2 are known to be associated with colon cancers. It has been well known that colorectal carcinogenesis is associated with serious oxidative stress and that catalase is decreased in colon carcinomas. However, the underlying molecular mechanisms remain elusive. Here, we report that Caudal-related homeodomain proteins positively regulate catalase expression in both Drosophila and humans. We found that Drosophila caudal heterozygotes have a decreased catalase expression and increased ROS generation in the hindgut, and that the overexpression of Caudal increases catalase promoter activity and catalase mRNA levels. We also found that CDX1 and CDX2 up-regulate catalase promoter activity and protein levels in HCT116 cells - human colorectal carcinoma cell lines. The level of catalase protein in several colorectal carcinoma cell lines was associated with CDX1 expression. These results suggest that CDX1 and CDX2 may be involved in intestinal homeostasis and tumorigenesis via regulation of catalase expression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.5
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• pp.518-524
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• 2008

Chromosome 18q alteration plays a key role in colorectal tumorigenesis, and loss of heterozygosity at 18q is associated with a poor prognosis in colon cancer. DCC(Deleted in Colorectal Cancer) is a putative tumor- suppressor gene at 18q21 that encodes a transmembrane protein with structural similarity to neural cell adhesion molecule that is involved in both epithelial and neuronal cell differentiation. DCC is implicated in regulation of cell growth, survival and proliferation. Thus, tumor progression in squamous cell carcinoma, stomach cancer, colorectal cancer correlates with downregulation of DCC expression. The mechanism for DCC suppression is associated with hypermethylation of the DCC gene promoter region. Hence, the goal of this study is to identify the promoter methylation responsible for the down-regulation of DCC expression in oral squamous cell carcinoma. 12 of tissue specimens for the study are excised and gathered from 12 patients who are diagnosed as SCC in department of OMS, dental hospital, dankook university. To find expression of DCC in each tissue samples, immunohistochemical staining, RT-PCR gene analysis and methylation specific PCR are processed. The results are as follows. 1. In the DCC gene RT-PCR analysis, 5(41.6%) of 12 specimens of oral squamous cell carcinoma did not expressed DCC gene. 2. In the promoter methylation specific PCR analysis, 5(41.6%) of 12 specimens showed promoter methylation of DCC gene. 3. In the immunohistochemical staining of poor differentiated and invasive oral squamous cell carcinoma, loss of DCC expression was observed. These findings suggest that methylation of the DCC gene may play a role in loss of gene expression in invasive oral squamous cell carcinoma.

• Molecules and Cells
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• v.39 no.4
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• pp.330-336
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• 2016

Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cance-rassociated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Reintroduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

• Journal of Life Science
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• v.28 no.7
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• pp.819-826
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• 2018

Orostachys japonicus (OJ) is a medicinal herb with immunoregulatory, anti-aging, anti-oxidative, and many other therapeutic properties. The purpose of this study was to elucidate the anti-cancer property of cultivated OJ. SW480 cell viability was significantly reduced by cumulative exposure to OJ extract. We also observed inhibitory effects of OJ after 72 hr through the growth and migration of SW480 cells using scratch assay. SW480 cells in OJ-free medium began to move into the scratch site at 24 hr; however, cells in medium containing OJ did not migrate into the scratch site until 48 hr. Male C57BL/6 mice (4 weeks old) were orally administered OJ extract for 31 days before injection of SW480 cells. At 7, 14, and 28 days after subcutaneous injection of SW480 cells, tumor weight and volume were analyzed. The body weight of the OJ-treated group was continuously increased during administration of the OJ extract relative to the control group. Injection of SW480 cells caused a reduction in body weight in all groups; however, the OJ-treated group exhibited a significant increase in body weight after 14 days. Tumor weight and volume were lower in the OJ-treated group than in the control group after 28 days. Although these results suggest that OJ suppresses the proliferation and migration of human colon cancer cells, additional studies are required to provide preclinical evidence before launching clinical trials evaluating OJ as an anti-cancer biohealth product.