• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.4
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• pp.726-731
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• 2000

This study was performed to evaluate the antitumor activities of water and ethanol (EtOH) extract of Salvia miltiorrhiza in vitro and in vivo. The proliferation of the human hepatoma (HepG2), rectum cancer (HRT-18) and colon cancer (HT-29) cells was inhibited by administration of extracts in a dose-dependent manner. Particularly, EtOH extract inhibited proliferation of the cells more effectively than water extract did. The morphology of cells induced by EtOH extract was characterized by reduction of cell size and deformatin. Oral administration of the EtOH extract (3 mg/head) to tumor-bearing mice inhibited the tumor (sarcoma-180) growth by 35% and prolonged their survival rate by 61%. The EtOH extract was shown to be nontoxic at 37.5% mg/head/day on the acute toxicity test. These studies suggest that the EtOH extract of Salvia miltiorrhiza may have antitumor activity in vitro and in vivo.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1615-1623
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• 2021

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.38 no.5
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• pp.281-285
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• 2005

Raw meat of mackerel (Scomber japonicus) was salted by refined, sun-dried, bamboo, and KC1-added bamboo salts. Antimutagenic activity on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Ames test and growth inhibitory effects of AGS human gastric and HT-29 human colon adenocarcinoma cells were investigated using methanol extracts of the salted mackerels. Mackerel salted sun-dried, bamboo, and KC1-added bamboo salts used increased the antimutagenic activities against MNNG, however, the sample treated with refined salt reduced the antimutagenic activity. Inhibitory effects of the salted-mackerels on the growth of human cancer cells were increased as dose dependent pattern. Mackerel salted with refined salt activated the growth of AGS human gastric adenocarcinoma cells, but mackerel salted with sun-dried, bamboo, and KC1-added bamboo salts kept or increased anticancer effect compared to the raw mackerel. Mackerel salted with KC1-added bamboo salt led to the highest antimutagenic and anticancer activities. These results suggest that antimutagenic and anticancer effects of mackerel during manufacturing of the salted-mackerel could be enhanced by using different kind of salts such as bamboo, or KC1-added bamboo salts.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.11
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• pp.1365-1370
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• 2007

The inhibitory effects of the water and methanol extracts of Jakwangdo and Honghyangmi on the rat microsome lipid peroxidation and growth of four human cancer cells such as HepG2 (liver cancer), SNU-1 (stomach cancer) MCF-7 (breast cancer) and SNU-C4 (colon cancer) were examined. The methanol extracts of red colored rices showed the antioxidant activity and growth inhibitory effects of cancer cells. However, water extracts did not show the activities. Inhibitory activities of methanol extracts of Jakwangdo and Honghyangmi against lipid peroxidation of rat microsome was 80% and 68%, respectively, at the concentration of 1 mg/assay. Jakwangdo methanol extracts showed the highest growth inhibitory activity in MCF-7 cells among the cancer cells tested. The methanol extracts of red colored rices were further fractionated with hexane, chloroform, ethyl acetate and butanol. Both chloroform and hexane fractions showed strong growth inhibitory activity in HepG2 and MCF-7 cells.

• Korean Journal of Food Science and Technology
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• v.30 no.6
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• pp.1470-1475
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• 1998

Two kinds of Korean rice-wine (Yakju) with different process and ingredients, and Japanese rice-wine (Sake) were chosen for this study, and throughly dried and solubilized in water or cell culture medium. In vitro cytotoxicity assays of the solubilized wine solids exhibited that maximum dilution factors for inhibition of B 16BL6 mouse melanoma cell growth were 16X for herbal medicine-added rice-wine (Korean rice-wine I) and typical Korean rice-wine (Korean rice-wine II), and 8X for Japanese rice-wine. Their cytotoxic effects on HRT18 human colon adenocarcinoma cells were even lower than those on B16BL6 cells. The morphology of the tumor cells were changed by addition of the solubilized wine solids. Inhibitory effect of the rice-wine on in vivo tumor growth and metastasis were monitored after implantation of B16BL6 cells into C57BL/6 mice with daily feeding the solubilized wine solids. Compared to non-fed control groups, B16BL6 tumor growth and metastasis to lung were clearly inhibited by feeding the wine solids, in order of Korean rice-wine I > Korean rice-wine II > Japanese rice-wine. The data of in vitro cytotoxicity and the cell shape changes indicate that the inhibitory effect of tumor progression may be attributed to tumor cell differentiation or immune stimulation induced by certain components in the rice-wine, rather than direct cytotoxicity of the components.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.7
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• pp.839-845
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• 2009

Colorectal cancer is the third most common malignant neoplasm in the world. Much attention has been focused on reducing colon cancer risk through medical properties of natural compound that could act as anticarcinogens. In this study, we evaluated the antioxidant and antigenotoxic effects of Styela plicata (S. plicata) from in vitro experiments. S. plicata extracts showed antioxidant activity measured by TRAP assay and antigenotoxic effect in $200{\mu}M$ $H_2O_2$ induced DNA damage in human leukocytes. Especially, freeze-dried S. plicata extracted with methanol showed the highest level of TRAP (0.225 mM) and inhibition of DNA damage (66.8%). Additionally we observed the effect of S. plicata on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) and DMH induced DNA damage (by comet assay) in male SD rats. The animals were divided into three groups and fed high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) without (normal control and DMH control) or with a 3% (w/w) of lyophilized S. plicata powder (DMH+S. plicata). One week after beginning the diets, rats were treated with DMH (30 mg/kg, s.c.) for 6 weeks except for normal control group, which was treated saline instead; dietary treatments were continued for the entire experiment. Nine weeks after DMH injection, administration of S. plicata resulted in reduction of ACF numbers, to 82.7% of the carcinogen control value ($7.67{\pm}2.04$ vs. $1.33{\pm}0.53$: p<0.01). S. plicata supplementation induced antigenotoxic effect on DMH-induced DNA damage in the blood cell (% tail intensity: $6.79{\pm}0.26$ vs. $6.13{\pm}0.22$). These data indicate that S. plicata extract has antigenotoxic and anticarcinogenic effects from in vitro experiments and S. plicata exerts a protective effect on the process of colon carcinogenesis, possibly by suppressing the DMH-induced DNA damage in blood cell and the development of preneoplastic lesions in colon.

• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.332-342
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• 1995

This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.

• Journal of Life Science
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• v.20 no.10
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• pp.1532-1537
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• 2010

This study compared the inhibitory effects of methanol extracts from yellow and black soybeans (black soybean, Seomoktae and Seoritae) on mutagenicity using the Ames test and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatments with the methanol extracts from either yellow or black soybeans in a dose dependent manner (p<0.05). The methanol extracts from various black soybeans tended to have a greater inhibitory effect compared to those from yellow soybeans. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from black soybean, Seomoktae and Seoritae showed 51%, 61% and 53% inhibitory rates, respectively, indicating that Seomoktae, a type of black soybean, had a stronger antimutagenic activity against mutagens (both $AFB_1$ and MNNG). Methanol extracts from black soybeans showed an inhibitory rate of greater than 50% on the growth of human cancer cells (AGS, HT-29 and Hep 3B) and the inhibition was more effective in the methanol extract from Seomoktae. Our results suggested that the methanol extracts from black soybeans showed stronger inhibitory effects on mutagenicity and growth of cancer cells than those from yellow soybean. It is concluded that intake of black soybean can be recommended for improving health.

• KSBB Journal
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• v.23 no.2
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• pp.177-182
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• 2008

In this study, crude extracts of the halophyte Limonium tetragonum and their solvent fractions were evaluated on anticancer activity in AGS and HT-29 human cancer cells using MTT assay. Each of the crude extracts (MeOH and $CH_2Cl_2$) of Limonium tetragonum showed a significant inhibitory effect on the growth of human cancer cells. The combined crude extracts of MeOH and $CH_2Cl_2$ were partitioned between $CH_2Cl_2$ and water. The organic layer was further partitioned between 85% aq. MeOH and n-hexane, and then the aqueous layer was fractionated with n-BuOH and $H_2O$, successively. Growth inhibition effects of crude extracts and their solvent fractions from Limonium tetragonum increased in a dose-dependent manner. Among them, 85% aq. MeOH, n-hexane and n-BuOH fractions revealed very good inhibition effects on the growth of human cancer cells. These results suggest that we can isolate active compounds from Limonium tetragonum to show much more strong anticancer activity.

• Journal of Yeungnam Medical Science
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• v.22 no.2
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• pp.166-182
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• 2005

Background: Cyclin-dependent kinase (CDK) inhibitors are family of molecules that regulate the cell cycle. The CDKN2, a CDK4 inhibitor, also called p16, has been implicated in human tumorigenesis. The CDKN2 inhibits the cyclin/CDK complexes which regulate the transition from G1 to S phase of cell cycle. There is a previous report that homozygous deletion of CDKN2 region on chromosome 9p21 was detected frequently in astrocytoma, glioma and osteosarcoma, less frequently in lung cancer, leukemia and ovarian cancer, but not detected in colon cancer and neuroblastoma. However, little is known about the relationship between CDKN2 and laryngeal cancer. Therefore this study was initiated to investigate the role of CDKN2 in human laryngeal squamous cell carcinoma development.1) Materials and methods: We used 5 human laryngeal carcinoma cell lines whether they have deletions or losses of CDKN2 gene expression by DNA-PCR or RT-PCR, respectively. We examined 8 fresh frozen human laryngeal cancer tissues to detect the loss of heterozygosity (LOH) of CDKN2. PCR was performed by using microsatellite markers of short arm of human chromosome 9 (D9S126, D9S144, D9S156, D9S161, D9S162, D9S166, D9S171, D9S200 and D9SIFNA). For informative cases, allelic loss was scored if the signal of one allele was significantly decreased in tumor DNA when compared to the same allele in normal DNA. Results: The CDKN2 DNA deletion was observed in 3 cell lines. The CDKN2 mRNA expression was observed in only one cell line, which was very weak. LOH was detected in 7 cases (87.5%). Conclusion: These results suggest that CDKN2 plays a role in the carcinogenesis of human laryngeal squamous cell carcinoma.