• Journal of Life Science
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• v.31 no.4
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• pp.400-409
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• 2021

Sanguinarine, a natural benzophenanthridine alkaloid, has been considered a potential therapeutic target for the treatment of cancer because it can induce apoptosis in human cancer cells; however, the underlying mechanisms of action still remain unclear. Tumor suppressor p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to anticancer agents. Therefore, in the present study, the role of p53 during apoptosis induced by sanguinarine was investigated in p53wild type (WT, p53+/+) and p53null (p53+/+) HCT116 colon carcinoma cells. Sanguinarine significantly caused greater reductions in cell viability in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells. Consistently, sanguinarine promoted more DNA damage and apoptosis in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells while increasing the expression of p53 and cyclin-dependent kinase inhibitor p21^WAF1/CIP1. Sanguinarine increased the activity of caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and it activated caspase-3, a typical effect caspase, in HCT116 (p53+/+) cells. Sanguinarine also increased the generation of reactive oxygen species (ROS), and the Bax/Bcl-2 ratio, while destroying the integrity of mitochondria in HCT116 (p53+/+) cells, but not in HCT116 (p53-/-) cells. Overall, the results indicate that sanguinarine induced p53-dependent apoptosis through ROS-mediated activation of extrinsic and intrinsic apoptotic pathways in HCT116 colorectal cancer cells.

• Journal of Life Science
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• v.25 no.4
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• pp.450-455
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• 2015

This study compared the heavy metal contents and the effects of extracts from domestic and imported red sea bream on the antioxidant activity and cytotoxicity of human cancer cell lines. The antioxidant activity was measured using the fluorescently sensitive dye, 2’-7’ dichlorofluorescein-diacetate (DCFH-DA), and antiproliferative activity against AGS human gastric adenocarcinoma and HT-29 human colon cancer cell lines, which was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Domestic red sea bream had a higher mercury content when compared to imported red sea bream, but there was no significant difference in the lead content. Treatments with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from domestic and imported red sea bream dose-dependently decreased the H₂O₂ induced ROS production, compared to the control. The cell viability showed that treatments with the A+M and MeOH extracts had cytotoxicity in the growth of AGS and HT-29 cancer cells. In the case of AGS, the extracts from the domestic red sea bream were higher in inhibiting cancer cell growth, compared to imported red sea bream. Our results demonstrate that the heavy metal contents of domestic and imported red sea bream were below the limit of the Food Code of Korea. The results of the biological activities indicate that the antioxidant activity of extracts from imported red sea bream was more effective, while the extracts from the domestic red sea bream were stronger in cytotoxic activity.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.685-691
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• 2005

Growth and DNA synthesis inhibitory effects of doenjang methanol extract and its solvent fractions on AGS human gastric adenocarcinoma cells, Hep 3B human hepatocellular carcinoma cells, HT-29 human colon cancer cells and MG-63 human osteosarcoma cells were studied. The treatment of doenjang methanol extract ($ 200{\mu}g/ml $) with the AGS, Hep 3B, HT-29 and MG-63 cancer cells after 6 days of incubation inhibited the growth of cancer cells by $32\%$, $51\%$, $84\%$ and $33\%$, respectively. To separate active compounds of doenjang, doenjang methanol extract was fractionated with dichloromethane, ethylacetate, and buthanol. Among the solvent fractions, the dichloromethane and ethylacetate fractions showed the highest growth inhibitory effects on various cancer cells. For example, the dichloromethane and ethylacetate fractions ($200a{\mu}g/ml$) sig-nificantly inhibited the growth of various cancer cells by $89\∼96\%$ and$62\∼86\%$, respectively. DNA synthesis of AGS and Hep 3B cancer cells was significantly inhibited by adding dichloromethane fraction ($200{\mu}g/ml$) up to $94\%$ and $80\%$, respectively. Similarly, the ethylacetate fraction ($ 200\mug/ml $) showed a $ 95\% $ inhibition rate of DNA synthesis in AGS cells. These results suggest that the dichloromethane and ethylacetate fractions have specific active compounds, which will explain this anticancer effect of doenjang.

• Journal of Life Science
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• v.19 no.12
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• pp.1737-1742
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• 2009

It has been known that Linum usitatissimum and Perilla frutescens are dietary sources of possible chemopreventive compounds such as lignans and $\alpha$-linolenic acid. Here, we investigated and compared the inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens 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 treatment with the methanol extract from either Linum usitatissimum or Perilla frutescens (p<0.05) in a dose dependent manner. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from Linum usitatissimum and Perilla frutescens showed 63% and 78% inhibitory rates, respectively, indicating that Perilla frutescens possessed stronger antimutagenic activity than did Linum usitatissimum. Inhibitory effects of methanol extracts from Linum usitatissimum and Perilla frutescens on the growth of human cancer cells (AGS, HT-29 and Hep 3B) appeared to increase dose dependently, and the inhibition was more effective against AGS and HT-29 compared to Hep 3B cells. Our results suggested that the methanol extract from Perilla frutescens showed stronger antimutagenic activity than that from Linum usitatissimumas assayed by the Ames mutagenic test, whereas the methanol extract from Linum usitatissimum was more effective than its counterpart for growth inhibition of human cancer cells. It is concluded that intake of Linum usitatissimum and Perilla frutescens as sources of omega-3 fatty acids will be beneficial for preventing cancer.

• Molecules and Cells
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• v.37 no.8
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• pp.620-627
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• 2014

We have previously shown that microRNAs (miRNAs) miR-760, miR-186, miR-337-3p, and miR-216b stimulate premature senescence through protein kinase CK2 (CK2) downregulation in human colon cancer cells. Here, we examined whether these four miRNAs are involved in the replicative senescence of human lung fibroblast IMR-90 cells. miR-760 and miR-186 were significantly upregulated in replicatively senescent IMR-90 cells, and their joint action with both miR-337-3p and miR-216b was necessary for efficient downregulation of the ${\alpha}$ subunit of CK2 ($CK2{\alpha}$) in IMR-90 cells. A mutation in any of the four miRNA-binding sequences within the $CK2{\alpha}3^{\prime}$-untranslated region (UTR) indicated that all four miRNAs should simultaneously bind to the target sites for $CK2{\alpha}$ downregulation. The four miRNAs increased senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal) staining, p53 and $p21^{Cip1/WAF1}$ expression, and reactive oxygen species (ROS) production in proliferating IMR-90 cells. $CK2{\alpha}$ overexpression almost abolished this event. Taken together, the present results suggest that the upregulation of miR-760 and miR-186 is associated with replicative senescence in human lung fibroblast cells, and their cooperative action with miR-337-3p and miR-216b may induce replicative senescence through $CK2{\alpha}$ downregulation-dependent ROS generation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.5
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• pp.516-523
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• 2006

The mushroom Inonotus obliquue (IO) has been traditionally used for the treatment of gastrointestinal cancer in Russia, Poland, and most of Baltic countries. To explore the possibility that IO has chemoprevention effects, we examined whether or not the aqueous extract of IO inhibits HT-29 cell growth and investigated tile mechanism for this effect. Cells were incubated in the presence of increasing concentrations of the aqueous extract of IO. The extract substantially inhibited the viable HT-29 cell number in a dose-dependent manner and inhibited 5-bromo-2'-deoxyuridine incorporation into DNA of HT-29 cells. Annexin-V staining followed by flow cytometry revealed that the extract induced apoptosis of HT-29 cells in a dose-dependent manner. Western blot analysis of total cell lysates revealed that the extract induced cleavage of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase, but did not affect the protein levels of Bax and Bcl-2. In addition, the extract dose-dependently increased the activity of caspase-8, -9 and -3. We have demonstrated that the aqueous extract of IO inhibits cell proliferation and induces apoptosis in HT-29 cells, which may be mediated by its ability to activate the caspase pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.437-443
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• 2003

Epidemiological data suggest that lycopene has anticancer activities in humans. Insulin-like growth factor-I receptor (IGF-IR) is a transmembrane tyrosine kinase that mediates the biological actions of IGFs and may play an active role in cancer progression. Because our previous in vitro studies have indicated lycopene inhibits HT-29 cell growth, the aim of this study was to determine whether lycopene induces apoptotic cell death and the inhibitory effect of lycopene on HT-29 cell growth is related to changes in IGF-IR levels and the receptor's intracellular signalling pathways. HT-29 cells were incubated for 4 days in serum-free medium in the presence of 0, 25, 50, or 100 $\mu$M lycopene, and the DNA fragmentation assay was performed. Cells treated with lycopene produced a distinct oligonucleosomal ladder with different sizes of DNA fragments, a typical characteristic of cells undergoing apoptosis. HT-29 cells were cultured for 4 days in serum-free medium in the presence of 0~100 $\mu$M lycopene and IGF-I (10nM) was added for 0~60 minutes immediately prior to lysate preparations. Western blot analysis of total lysates revealed that lycopene decreased the levels of IRS-1, Akt, phosphatidylinositol 3-kinase (PI3K), and IGF-IR $\beta$-subunit, and increased the levels of the IGF-IR precursor dose dependently. Lycopene also decreased IGF-I-induced phosphorylation of IGF-IR$\beta$, IRS-1 and Akt, which were, at least in part, due to decreased expression of these proteins. These results suggest that lycopene induces apoptosis of HT-29 cells by inhibiting IGF-IR signaling thereby interfering with an IGF-II-driven autocrine growth loop, which is known to exist in this cell line.

• Journal of Life Science
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• v.28 no.6
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• pp.733-737
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• 2018

Cucurbitacin-I, a natural triterpenoid derived from Cucurbitaceae family plants, exhibits a number of potentially useful pharmacological and biological activities. Indeed, the previous study demonstrated that cucurbitacin-I reduced the proliferation of colon cancer cells by enhancing apoptosis and causing cell cycle arrest at the G2/M phase. CD44, a type I transmembrane protein with the function of adhering to cells, mediates between the extracellular matrix and other cells through hyaluronic acid. Recent studies have demonstrated that an overexpression of the CD44 membrane receptor results in tumor initiation and growth, specific behaviors of cancer stem cells, the development of drug resistance, and metastasis. The aim was to examine the effect of cucurbitacin-I on CD44 expression human ovarian cancer cells because the effect of cucurbitacin-I on CD44 expression has not been reported. The expressions of CD44 mRNA and protein were detected using a quantitative real-time reverse-transcription polymerase chain reaction and a Western blot analysis, respectively. Treatment with cucurbitacin-I inhibited the expression of CD44 mRNA and protein. A subsequent analysis revealed that cucurbitacin-I blocked the phosphorylation of activator protein-1 (AP-1) and nuclear factor kappa-B ($NF-{\kappa}B$), which are key regulators of CD44 expression. Taken together, the data demonstrate that cucurbitacin-I regulates the AP-1 and $NF-{\kappa}B$ signaling pathways, leading to decreased CD44 expression.

• Journal of Life Science
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• v.17 no.10
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• pp.1368-1373
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• 2007

Inhibitory effects of several solvent fractions from soybean on mutagenicity using Salmonella typhimurium TA 100 in Ames test and growth of human cancer cells (AGS gastric adenocarcinoma, Hep 3B hepatocellular cancinoma and HT-29 colon cancer cells) were studied. The treatment of dichloromethane and ethylacetate fractions (2.5 mg/assay) extracted from soybean to Ames test system inhibited aflatoxin $B_1\;(AFB_1)$ induced mutagenicity by 83%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N#-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 67%) among solvent extracts, although the inhibitory effect was not stronger compared with $AFB_1$ induced mutagenicity. In sulforhodamine B (SRB) assay, the treatment of ethylacetate fraction (2 mg/assay) significantly inhibited the growth of AGS, Hep 3B and HT-29 cancer cells by 66%, 73% and 77%, respectively, followed with the intermediate and dichloromethane fractions. These results indicated that soybean fraction extracted with ethylacetate had higher inhibitory effects on $AFB_1$ and MNNG in Ames test and growth inhibition activity to human cancer cells was appeared, suggesting that soybean fraction extracted with ethylacetate may contain the biologically active compounds.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.48
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• pp.58-64
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• 2003

To enjoy a healthy life, it is important to have a well-balanced diet. However, in today's society, there is an increase in the consumption of preprocessed foods and frequency of eating out. Also the western diet, which is becoming move popular worldwide, contains relatively high levels of protein and fat, and a low amount of fiber, Furthermore, the increased availability of favorite foods has created a condition were the individual diet is less variable. With these conditions, it is difficult to maintain a diet that is nutritionally balanced. With these unbalanced diets, which are difficult to change, there has been an increase in adult disease and health problems, such as colon and breast cancer, It is speculated that metabolites for carcinogens are produced from diet components and that intestinal bacteria contribute to the production of these metabolites. Therefore, it is necessary to evaluate the relationships between health, diet, and intestinal microflora. Soybean oligosaccharide is composed of water-soluble saccharides that have been extracted from soybean whey, a by-product from the production of soy protein. This is mainly a mixture of mono-, di-, tri-, and tetrasac-charides, with the principle components being the oligosaccharide raffinose and stachyose. When consumed by humans, the oligosaccharides cannot be digested in the human duodenal and small intestinal mucosa, and these are selectively utilized by beneficial bifidobacteria in intestines. The results of acute and subacute toxicity tests, soy-bean oligosaccharides were nonpoisonous. Soybean oligosaccharides promote the growth of indigenous bifido-bacteria in the colon which by their antagonistic effects, suppress the activity of putrefactive bacteria. Also, they reduce toxic metabolites, detrimental enzymes and plasma lipid, and increase in the frequency of bowel evacuation and fecal quantities. Consequently, soybean oligosaccharides as functional foods components have potential roles in the prevention and medical treatment of chronic adult diseases. The study of processing property and physiological function of soybean oligosacchavides and development of high oligosaccharide variety allow the creation of new and exciting foodstuffs that aye functional healthy.