• YAKHAK HOEJI
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• v.48 no.3
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• pp.189-196
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• 2004

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

• Journal of Nutrition and Health
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• v.26 no.7
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• pp.829-838
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• 1993

This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.6-16
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• 2013

Recent estimates for colon cancer incidence in Korea have been increased and continue to rank as the second most common in male and the third in female. Although colonoscopy has been known as the best screening tool for colon cancer, 20-25% of patients with colon cancer was diagnosed with stage IV cancer. During the past 10 years, intensive clinical studies helped to establish the value of palliative treatment for colon cancer with metastasis. The introduction of new chemotherapeutic agents such as irinotecan and oxaliplatin has led to a significant increase in tumor response and median survival. In advanced colon cancer, impressive prolongation or overall survival can be achieved through sequential application of combined systemic chemotherapy. In addition, targeted manipulation of molecular tumor mechanisms with new substances such as monoclonal antibodies against the epidermal growth factor receptor or vascular endothelial growth factor shows promising effects. Progress in the systemic treatment of colon cancer is evident, not only because of the significant increase in life expectancy in advanced colon cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.8
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• pp.1100-1105
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• 2012

Green tea intake is known to have preventive effects against cancer. In this study, we evaluated the tumor suppressive effects of dietary green tea extracts (GTE) as a modulator on cisplatin in an established colon cancer mouse model. The cisplatin-induced cytotoxicity was determined with cell viability of the mouse colon cancer cell line (CT26) in vitro. The influence of GTE on the anti-tumor activity of cisplatin was evaluated by measuring tumor size with digital calipers in mice bearing CT26 colon carcinomas. The CT26 cell viability decreased to 93% at a $20{\mu}g/mL$ concentration of cisplatin. However, cell viability decreased to 15% with a combination of $20{\mu}g/mL$ cisplatin and GTE ($75{\mu}g/mL$). There were no apparent changes in cisplatin-induced cytotoxicity with GTE and epigallocathechin gallate (EGCG) treatments. Tumor size decreased in dietary GTE combining intra-peritoneal cisplatin-injected tumors bearing mice compared with cisplatin or GTE alone administered to tumor-bearing mice. These experiments showed that dietary GTE has a potentiating effect on the cisplatin anti-tumor activity of an established mice colon cancer model. Therefore, the GTE may be a candidate for modulators in anticancer treatments with cisplatin.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.127-131
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• 2000

Previously, we have reported an antitumor efficacy of liposomal N-(phosphon-acetyl)-L-aspartic acid (or PALA) in C-26 tumor bearing Balb/c mice, where PALA in liposome was administered one day after tumor inoculation. In this report, we have investigated the therapeutic potency of liposomal formulation of PALA, which was administered eight days after tumor inoculation in the same C-26 tumor bearing mice. The C-26 murine colon tumor inoculated mice were randomized for the in vivo therapy and the survival was measured after a single intraperitoneal injection of the drug. When the therapy was initiated eight days after tumor inoculation, DSPC-PALA at 150 mg/kg resulted in a significant increase in median survival time (MST) of 56% over the control group which received MES/HEPES buffer alone. However, none of the free PALA and DSPG-PALA liposome doses caused a statistically significant increase in MST over control group at the 95% confidence level. At 750 mg/kg dose, free PALA caused a marginally significant improvement in MST by 34%, but both 375 mg/kg and 150 mg/kg doses of free PALA caused only a 2% and a 4% increase in MST, respectively. These results show that PALA in neutrally charged liposome can exhibit considerably greater potency than free PALA in established C-26 tumor bearing mice.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.145-153
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• 2006

Background: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. Methods: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. Results: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. Conclusion: In two different colon cancer cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher agspecific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.861-867
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• 2003

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 $\mu$ g/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity. i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

• Biomedical Science Letters
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• v.19 no.4
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• pp.303-309
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• 2013

Oncolytic vaccinia virus is an engineered vaccinia virus that selectively destroys cancer cells and induces tumor immune response. Oncolytic vaccinia expressing mouse GM-CSF showed cytotoxic activity against various kinds of cancer cells when oncolytic vaccinia virus expressing human GM-CSF and mouse GM-CSF is intravenously administered in the mouse CT26 colon tumor model. Cancer cells treated with isolated immunoglobulin G from the serum with complement showed these cytotoxic activity and complement observed dose-dependent cytotoxic effect. These results suggest that oncolytic vaccinia virus expressing mouse GM-CSF can increase oncolytic vaccinia virus by inducing anticancer antibody in a mouse tumor model. Further studies are needed on antitumor immunity of GM-CSF.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.266-274
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• 2022

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.

• Journal of Integrative Natural Science
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• v.16 no.3
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• pp.81-95
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• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.