• Journal of Ginseng Research
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• 제35권3호
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• pp.315-324
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• 2011

This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without $100{\mu}g/L$ PMA in the absence or presence of various concentrations (100, 200, or $300{\mu}g/mL$) of red ginseng extract. Red ginseng extract treatment caused signifi cant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were signifi cantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity signifi cantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.

• International Journal of Oral Biology
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• 제45권3호
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• pp.134-142
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• 2020

Colon cancer is one of the most common malignant tumors, but there are still a few validated biomarkers of colon cancer. Exosome-mediated microRNAs (miRNAs) have been recognized as potential biomarkers in cancers, and miRNAs can regulate a variety of genes. Recently, Fusobacterium nucleatum was discovered in the tissues of human colon cancer patients. Its role in colon cancer was highlighted. F. nucleatum may contribute to the progression of colon cancer through the mechanism of exosome-mediated miRNAs transfer. However, the exosomal miRNAs regulation mechanism by F. nucleatum in colon cancer is not well known. Thus, we performed next-generation sequencing to investigate the overall pattern of exosomal miRNAs expression in the colon cancer cell culture supernatant. We have confirmed the alterations of various exosomal miRNAs. In addition, to investigate the function of exosomal miRNAs, a Kyoto Encyclopedia of Genes and Genomes analysis was performed on the target genes of changed miRNAs. Potential target genes were associated with a variety of signaling pathways, and one of these pathways was related to colorectal cancer. These findings suggested that F. nucleatum can alter exosomal miRNAs released from colorectal cancer cells. Furthermore, exosomal miRNAs altered by F. nucleatum could be potential biomarkers for the diagnosis and therapy of colon cancer.

• 약학회지
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• 제48권3호
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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 Ginseng Research
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• 제10권2호
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• pp.141-150
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• 1986

This study was attempted to screen the cytotoxic activity of petroleum ether ex- tract from panax ginseng root against human colon cancer cells. Two extracts of panax ginseng root, crude and partially purified, were used for this experiment. The crude extract was prepared by extraction with petroleum ether using Soxhlet aparatus for 12 to 15 hours from panax ginseng and the extract was partially purified by silicic acid column with mixture of petroleum ether: ethyl ether (70 : 30, v/v). Three species of human colon cancer cells, HRT-18, HCT-48 and HT-29, were maintained in DMEM (Dulbecco's modified Eagle medium), and the cells were cultured in DMEM containing serial concentration of the crude or partially purified fraction to observe the cytotoxic activity of the both extracts. The effects of incubation time and concentration of the both extracts in culture medium against the growth of the each cancer cell were determined. The results obtained are summarized as follows: 1. The doubling times of the HRT-18, HCT-48 and HT-29 cells were about 20, 24 and 22 hours, respectively. 2, The inhibitory effects of the crude extract on the growth of cancer cells were increased according to the rise of concentration of the extract and incubation time. 3. The inhibitory effect of partially purified fraction on the growth of HRT-18 cell was about 4 times stronger than that of the crude extract under same experimental condition. 4 The inhibitory effects of the crude and purified fraction on the growth of each cancer cell were shown difference by the kind of the cancer cell. In view of the above results, it could be said that the petroleum ether extract of panax ginseng root inhibited the division of the human colon cancer cell, in vitro.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1987년도 Proceedings of Korea-Japan Panax Ginseng Symposium 1987 Seoul Korea
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• pp.29-37
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• 1987

This study was devised to observe the cytotoxlc activities of petroleum-ether extract of Panax ginseng root(crude Gx) and its partially purified fraction from silicon acid column chromatography(7:3 CX) against sarcoma-180(5-180) and Walker carcinosarcoma 256(Walker 256) in vivo, and murine leukemic lymphocytes(L1210) and human rectal cancer cell(HRT-18) and human colon cancer cells(HT-29 and HCT-48) in vitro . Each cell-line was cultured in medium containing serial concentrations of the crude Gx or 7:3 Gx in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro In the meantime, ginseng saponin derivatives did not cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7:3 Gx was about 3 times more potent than that of crude Gx, one unit of cytotoxic activity against L121f cells being equivalent to 2.54$\mu\textrm{g}$ and 0.88 $\mu\textrm{g}$ for the crude Gx and 7:3 Gx, respectively. The Rf value of the active compound on silica -gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90:10:1, v/v/v) as a developing solvent was 0.23. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7:3 Gx treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gx. The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude Gx, which can explain a part of the origin of its anticancer activity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1871-1877
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• 2014

Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells.

• Preventive Nutrition and Food Science
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• 제5권2호
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• pp.114-118
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• 2000

The inhibitory effects of doenjang extracts and linoleic acid(LA) which was identified as one of the active compounds in doenjang on the growth of human cancer cells were studied, comparing to the actions on normal cells. Methanol extract and hexane fraction from doenjang exhibited the strong growth inhibitory effect on HT-29 human colon carcinoma cells. Inhibitory effects of chloroform, ethyl acetate, butanol and aqueous fractions on the cancer cells were observed, moderately or weakly. When cell counts of SNU-C$_1$human colon carcinoma cells were determined daily for 6 days, the inhibitory effect of hexane fraction on this cell line was higher than that of the methanol extract from doenjang. LA completely suppressed the growth of SNU-C$_1$cells after 4 days, while conjugated linoleic acid(CLA) resulted in 98% inhibition after 6 days. With the addition of LA and other free fatty acids such as stearic acid, oleic acid, linolenic acid and ${\gamma}$-linolenic acid (${\gamma}$-LnA) to the culture system, the growth of HT-29 cells and SNU-C$_1$cells was greatly suppressed after 6 days. Inhibitory effects of LA ${\gamma}$-LnA on the growth of these cells were stronger than other fatty acids. On the growth of AZ-521 human gastric carcinoma cells, LA and CLA completely cuppressed the growth of the cells after 4 days and 3 days, respectively. At the level of 0.001%~0.01% of LA, there was no cytotoxic effect on normal rat kidney cells and normal intestine human cells. These results showed that LA, a major active compound of doenjang, had strong inhibitory effects on the growth of human cancer cells without damaging normal cells.

• 한방안이비인후피부과학회지
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• 제24권1호
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• pp.16-24
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• 2011

Objective : In this study, we investigated the effects of ethanol extract of Anemarrhenae Rhizoma (EAR) on the proliferation and apoptosis induction of HT-29 human colon cancer cells. Methods : Cell viability of HT-29 cells were measured by MTT assay and apoptisis-related proteins were assessed using western blotting. Chromatin condensation of HT-29 cells stained with Hoechst 33258. Results : In the present study, we demonstrated that EAR exhibited significant cytotoxicity in HT-29 cells. The induction of apoptosis in HT-29 cells by EAR treatment was characterized by chromatin condensation and the activation of caspase-3. EAR-induced apoptosis is accompanied by the release of cytochrome c and the specific proteolytic cleavage of PARP. EAR was appeared cytotoxic effect to HT-29 cells in a dose-dependent manner. Concomitantly, EAR treatment led to increase in the caspase-9. The reduction of Bcl-2 and truncation of Bid were induced by EAR. Conclusion : We studied that the EAR induced apoptosis in human colon adenocarcinoma HT-29 cells. These results indicated that EAR can cause apoptosis through mitochondria/caspase pathway in human HT-29 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.2987-2991
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• 2014

Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.

• Biomolecules & Therapeutics
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• 제30권2호
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• pp.137-144
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• 2022

Radiation resistance represents an imperative obstacle in the treatment of patients with colorectal cancer, which remains difficult to overcome. Here, we explored the anti-proliferative and migration-inhibiting properties of the natural product shikonin on a radiation-resistant human colon carcinoma cell line (SNU-C5RR). Shikonin reduced the viability of these cells in a dose-dependent manner; 38 µM of shikonin was determined as the half-maximal inhibitory concentration. Shikonin induced apoptotic cell death, as demonstrated by increased apoptotic body formation and the number of TUNEL-positive cells. Moreover, shikonin enhanced mitochondrial membrane depolarization and Bax expression and also decreased Bcl-2 expression with translocation of cytochrome c from mitochondria into the cytosol. In addition, shikonin activated mitogen-activated protein kinases, and their specific inhibitors reduced the cytotoxic effects of shikonin. Additionally, shikonin decreased the migration of SNU-C5RR cells via the upregulation of E-cadherin and downregulation of N-cadherin. Taken together, these results suggest that shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in SNU-C5RR cells.