• Korean Journal of Food Science and Technology
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• v.52 no.6
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• pp.616-621
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• 2020

Sinapinic acid is a widely-distributed phenolic acid in various edible plants. In this study, changes in chemical stability and biological activities of sinapinic acid by heat treatment were evaluated at different pH values. The decomposition of sinapinic acid with heating at 95℃ was accelerated at higher pH; the residual levels after 10 min of heating were 80, 45 and 24% at pH 6, 7 and 8, respectively. Levels of reactive oxygen species derived from sinapinic acid also increased after heating at pH 7 and 8. ABTS radical scavenging activities and ferric reducing antioxidant power of sinapinic acid were reduced significantly after heating at pH 7 and 8. The cytotoxic activity of sinapinic acid against HCT116 cells was significantly enhanced after heating at pH 8 with decreased glutathione levels. The results suggest that heat treatment causes changes in the chemical stability and biological activities of sinapinic acid, and such changes are more prominent at higher pH.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.594-601
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• 2015

In the present study, the total content of polyphenols and flavonoids, the antioxidant activities, and cytotoxic effects of the ethanol extracts from different parts of Taraxacum coreanum Nakai were investigated for their use as functional foods. The extract yields of the flower, leaf, and root were $32.15{\pm}3.21%$, $31.63{\pm}0.63%$, and $27.48{\pm}2.47%$, respectively. Total polyphenol and flavonoid content of the flower extract were $61.29{\pm}2.11mg/g$ and $46.11{\pm}1.88mg/g$, respectively, which were much higher than those of any other plant parts. The antioxidant activities of the flower, leaf, and root extracts were $89.99{\pm}2.83%$, $85.29{\pm}2.22%$, and $37.88{\pm}2.34%$, respectively, at a concentration of 1.0 mg/mL. Cell cytotoxicity effects of AGS (human gastric carcinoma), HCT116 (human colon carcinoma), and A549 (human pulmonary carcinoma) cells were the highest in the flower extract, with values of $62.85{\pm}4.63%$, $69.89{\pm}3.44%$, and $85.72{\pm}4.17%$, respectively, at a concentration of 400 mg/kg. Both the antioxidant activities and cytotoxic effects of the ethanol extracts from all the parts of the T. coreanum Nakai increased dose-dependently. These results provide preliminary data for the development of T. coreanum Nakai as an edible functional food material.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.1
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• pp.79-92
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• 2006

This study was carried out to evaluate antioxidative, cytotoxic and chemosensitizing effects for anti-tumor activities of Naesosungma-tang (NST). The results were as follows ; 1. The oxidative effects were measured by DPPH radical scavenging activity. NST water extract was showed more effective than ethanol extract and also various solvent fractions from NST showed effective in the following order : butanol fraction > ethyl acetate fraction > hexane fraction > aqueous fraction. 2. NST water extract was showed cytotoxic effects on the human cancer cells Calu-6 cell and SNU-601 cell, but not on MCF-7 cell. 3. The viability of cells was measured in 4 kinds of solvent fractions from water extract of NST by MTT assay. The results were as followings : 1) On the NIH3T3 cell, $IC_{50}$ value was $200{\sim}300\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 2) On the Caco-2 cell, effective only in the butanol fraction. 3) On the Calu-6 cell, most effective in hexane fraction($IC_{50}:80\;{\mu}g/m{\ell}$) and effective in ethyl acetate and butanol fraction($IC_{50}:100{\sim}120\;{\mu}g/m{\ell}$). 4) On the MCF-7 cell, $IC_{50}$ value was similar in three fractions except aqueous fraction. 5) On the SNU-601 cell, $IC_{50}$ value was within $100\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 6) On the HCT-1l6 cell, $IC_{50}$ value was $150{\sim}200\;{\mu}g/m{\ell}$ in three fractions except aqueous fraction. 7) On the AML-2/WT cell, not effective in four kinds of solvent fractions. 4. In combined effects of NST and vincristine on AML-2/D100 cell, water and ethanol extracts of NST and hexane fraction of water extracts of NST more effectively inhibited proliferation of AML-2/D100 cell. These results Suggest that NST has antioxidative and cytotoxic effects against Caco-2, Calu-6, MCF-7, SNU-601, HCT116 and NIH3T3 cell especially Calu-6 and SNU-601 cell, and also chemosensitizing effects against AML-2/D100 cell in combined vincristine.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4045-4048
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• 2014

Effects of transforming growth factor-beta (TGF-${\beta}$) were investigated in human colorectal cancer, and the influence of cantharidinate in inhibiting TGF-${\beta}1$ expression was explored. Relationships among TGF-${\beta}1$ and sex, age, tumor size, tumor location, tumor stage were also analyzed. H&E and immunohistochemistry staining were employed to assess colorectal cancer and TGF-${\beta}1$ expression, respectively. Then, HCT-116 CRC cells were randomly divided into four groups, controls, no serum-treated, chemotherapy and cantharidinate-treated. Immunohistochemistry and real-time PCR were employed to assess the expression of TGF-${\beta}1$ in CRC cells. Our data showed that the expression of TGF-${\beta}1$ might be associated with tumor size and tumor location (P<0.05). The expression of TGF-${\beta}1$ in CRC groups was higher than in adjacent groups (P<0.05). In addition, the expression of TGF-${\beta}1$ in cantharidinate-treated group was much lower than in CRC group (P<0.05). Taken together, these results suggest that TGF-${\beta}1$ plays an important role in CRC development. Cantharidinate might inhibit the expression of TGF-${\beta}1$ and control the development of colorectal cancer.

• BMB Reports
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• v.53 no.5
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• pp.272-277
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• 2020

Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21^Cip1/WAF1 pathway. The transcription factor "nuclear factor erythroid 2-related factor 2" (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21^Cip1/WAF1 in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S-transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activated protein kinase (AMPK). Collectively, our data suggest that both Keap1 stabilization and AMPK inactivation are associated with decreased activity of Nrf2 in CK2 downregulation-induced cellular senescence.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2061-2068
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• 2015

Background: Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Materials and Methods: Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of $600mm^3$ to $700mm^3$. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). Results: The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Conclusions: Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

• Korean Journal of Plant Resources
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• v.30 no.6
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• pp.640-646
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• 2017

In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

• Molecules and Cells
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• v.43 no.3
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

• Journal of Life Science
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• v.29 no.10
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• pp.1062-1070
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• 2019

A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

• The Korea Journal of Herbology
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• v.22 no.3
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• pp.27-37
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• 2007

Objectives: Hepatocellular carcinoma is the most common primary malignant tumor of the liver worldwide. In-Jin-Ho-Tang(IJHT) has been used as a traditional Chinese herbal medicine since ancient time. and today it is widely applied as a medication for jaundice which is associated with inflammation in liver. In this study, I investigated whether methanol extract of IJHT induced HepG2 cancer cell death. Methods: Cytotoxic activity of IJHT on HepG2 cells was using XTT assay. Apoptosis induction by Ros A in HCT116 cells was verified by the induction of cleavage of poly ADP-ribose polymerase (PARP). and activation of caspase-3, -8 and -9. The release of cytochrome c from mitochondria to cytosol. the level of Bcl-2 and Bax and the expression of p53 and p21 were examined by western blotting analysis. Furthermore, MAPKs activation was analyzed by western blotting analysis. Results: IJHT induced apoptosis in HepG2 cells. And treatment of IJHT resulted in the release of cytochrome c into cytosol, decreased anti-apoptotic Bcl-2, and increased pri-apoptotic Bax expression. IJHT markedly inactivated extracellular signal-regulated kinase (ERK1/2), and activated p38 mitogen-activated protein (MAP) kinase. Sodium orthovanadate (SOV), a phosphatase inhibitor, to reverse IJHT-induced ERK1/2 inactivation and SB203580, a specific p38 MAP Kinase inhibitor efficiently blocked apoptosis of HepG2. Thus, IJHT induces apoptosis in HepG2 cells via MAP kinase modulation. Conclusion: These results indicated that IJHT has some potential for use as an anti-cancer agent.