• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7561-7566
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• 2015

Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary diseases. However, its dietary effect on chemoprevention of colon cancer has never been studied. The present study was to evaluate the protective effects of dietary ZJ on colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between was administered to induce colitis-associated colon cancer. ZJ fruit was supplemented in feed as 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation thereby decreasing the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation delayed the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leucocytes, main regulators of cancer inflammation. Therefore, dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

• IMMUNE NETWORK
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• v.12 no.5
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• pp.189-195
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• 2012

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanisms are still largely unknown. The incidence of colon cancer is now increasing in Korea. Therefore, we have examined here the effect of vitamin C on the induction of the apoptosis on colon cancer and its related mechanisms. We have found that remarkable increase of the apoptosis and the calcium influx in endoplasmic reticulum (ER) in human colon cancer cell line, HCT-8. However, vitamin C-induced apoptosis was effectively inhibited by the pre-treatment of BAPTA-AM (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), which is well-known as a calcium specific chelator. During the apoptosis, we found the increase of the translocation of Bad to mitochondria from cytosol, after releasing from 14-3-$3{\beta}$. In this process, the expression of Bax, a well-known pro-apoptotic protein, was also increased. Taken together, vitamin C induces apoptosis of colon cancer cell line, HCT-8 through the increase of 1) the calcium influx in endoplasmic reticulum (ER), 2) the translocation of Bad to mitochondria, and 3) the expression of Bax.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.402-410
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• 2010

Although the overproduction of prostaglandin $E_2$ ($PGE_2$) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying $PGE_2$-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating $PGE_2$-mediated signaling pathway. $PGE_2$ stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK. $PGE_2$ also increased the phosphorylation of GSK-$3{\beta}$, the translocation of ${\beta}$-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited $PGE_2$-induced growth stimulation and also suppressed $PGE_2$-mediated signal transduction, as well as ${\beta}$-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5823-5828
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• 2015

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

• IMMUNE NETWORK
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• v.10 no.6
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• pp.206-211
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• 2010

Background: Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of colon cancer because it has been recurred and produced few side effects in patients. Secretory glycoprotein 90K has been found at elevated level in various cancer tissues and sera. We investigated to establish a more effective DC vaccine for the treatment of colon cancer in which the levels of 90K are elevated. Methods: We obtained the concentrated 90K from 293T cells stably expressing 90K. DCs were cultured from peripheral blood monocytes, and a DC vaccine pulsed with tumor lysate was compared with a DC vaccine pulsed with 90K. We measured the functional activity for CTLs by using IFN-${\gamma}$-enzyme linked immunoabsorbent spot (ELISPOT) assay. Results: DCs pulsed with tumor lysate+90K exhibited the enhanced T cell stimulation, polarization of $\ddot{i}$ T cell toward Th1. The CTLs generated by DCs pulsed with 90K efficiently lysed HCT116 cells. The results indicate that 90K-speicifc-CTLs can recognize 90K proteins naturally presented by colon cancer cells. Conclusion: Our study suggests that 90K-specific CTLs generated by 90K-pulsed DCs could be useful effector cells for immunotherapy in colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5501-5508
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• 2014

Luteolin, 3', 4', 5,7-tetrahydroxyflavone, belongs to a group of naturally occurring compounds called flavonoids that are found widely in the plant kingdom. It possesses many beneficial properties including antioxidant, anti-inflammatory, anti-bacterial, anti-diabetic and anti-proliferative actions. Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Many signaling pathways are deregulated during the progression of colon cancer. In this review we aimed to analyze the protection offered by luteolin on colon cancer. During colon cancer genesis, luteolin known to reduce oxidative stress thereby protects the cell to undergo damage in vivo. Wnt/${\beta}$-catenin signaling, deregulated during neoplastic development, is modified by luteolin. Hence, luteolin can be considered as a potential drug to treat CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.753-756
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• 2015

Background: Red cell distribution width (RDW) is one of the standard parameters with blood cell counts. Much previous research has indicated that it increases in cases of systemic inflammation or cardiametabolic incident. However, information on the relation of RDW with solid tumors causing systemic inflammation is limited. In the present research, we examined the relation of RDW with malignant and benign lesions of the colon. Materials and Methods: 115 patients with colon polyps (group 1), and 30 with colon cancer (group 2) who were diagnosed histopathologically in our clinic between January 2010-January 2013 were scanned retrospectively. Patients with anemia, hematologic diseases and active inflammation were excluded. RDW, mean corpuscular volume (MCV), hemoglobin (Hgb) and platelet (Plt) measurements were recorded and their relations with the malignant and benign lesions of the colon were examined. Results: Both groups were similar in age and gender distribution. RDW values of patients with colon cancer were significantly higher than the patients with colon polyp (p=0,01). No significant differences were detected between the two groups in terms of MCV and Plt values (p>0,05). Conclusions: RDW can be used as an early warning biomarker for solid colon tumors. Further prospective research is required on the relations of cheap and easily measured RDW parameters with colon malignancies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8581-8586
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• 2014

Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-${\beta}$) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.

• Journal of Microbiology and Biotechnology
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• v.14 no.5
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• pp.891-900
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• 2004

UDP-N-Acetylglucosamine(GlcNAc):$\beta$1,4-D-mannoside$\beta$-l ,4N-acetylglucosaminyltransferase-III (GnT-III) and UDP-N-GlcNAc:$\alpha$-6-D-mannosid$\beta$-1,6N-acetylglucosaminyltransferase-V(GnT - V) activities were determined in human hepatoma cell lines and metastatic colon cancer cells, and their activities were compared with those of normal liver cells and fetal hepatocytes. GnT-III activities were higher than those of GnT-V in hepatic carcinoma cells. When the two enzyme activities were assayed in highly metastatic colon cancer cells, GnT - V activities were much higher than those of GnT-III. When GlcN, GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins had characteristically very low levels of GnT-III and -V activities, whereas hepatoma and colon cancer cells contained high levels of activities. These data were supported by RT-PCR and Northern blot analyses, showing that the expression of GnT-III and -V mRNAs were increased in proportion to the enzymatic activities. The increased GnT-III, md -V activities were also correlated with increased glycosylation of the cellular glycoproteins in hepatoma and colon cancer cells, as examined by lectin blotting analysis by using wheat germ glutinin (WGA), erythroagglutinating phytohemagglutinin (E-PHA), leukoagglutinating phytohemagglutinin (L-PHA), and concanavalin A (Con A). Treatment with retinoic acid, a differentiation agent, resulted in decreases of both GnT-III and -V activities of HepG2 and HepG3 cells. In colon carcinoma cells, however, treatment with retinoic acid resulted in a reduction of GnT-V activity, but not with GnT-III activity. Although the mechanism underlying the induction of these mzymes is unclear, oligosaccharides in many glycoproteins have been observed of cancer cells.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.471-478
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• 2015

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.