• Natural Product Sciences
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• v.23 no.4
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• pp.265-269
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• 2017

Pseudolaric acids of Pseudolarix kaempferi (Pinaceae) have been known as diterpenoids with potent anti-fungal-, anti-microbial, and cytotoxic activities. In the present study, the five MeOH extracts were prepared from the five plant part (root bark, stem bark, leaf, the inner part of root, and cone) to find the relation between the concentration of pseudolaric acids and cytotoxicity. Pseudolaric acids B and C were isolated from the root bark of P. kaempferi to use them as standard compounds. The five extracts were tested on cytotoxicity against six cancer cell lines, A549 (lung), HCT116 (colon), MDA-MB-231 (breast), SNU638 (stomach), and SK-hep-1 (liver) by SRB assay, but against K562 (leukemia) by SRB- or MTT assay. HPLC quantification were performed on a Shisheido Capcell PAK C18 column ($5{\mu}m$, $4.6mm{\times}250mm$) using 254 nm wavelength. The cytotoxicity ($IC_{50}$, $0.36{\mu}g/ml$ on K562 cell lines) of the root bark extract was potent and the content (101.1 mg/g extract) of pseudolaric acid B was very high in the root bark. These results suggest that the MeOH extract obtained from the root bark could be developed as the anti-cancer agent with a high quantity of pseudolaric acid B.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• 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.

• 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.

• Natural Product Sciences
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• v.21 no.3
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• pp.162-169
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• 2015

Hamamelis japonica (Hamamelidaceae), widely known as Japanese witch hazel, is a deciduous flowering shrub that produces compact clumps of yellow or orange-red flowers with long and thin petals. As a part of our ongoing search for phenolic constituents from this plant, eleven phenolic constituents including six flavonol glycosides, a chalcone glycoside, two coumaroyl flavonol glycosides and two galloylated compounds were isolated from the flowers. Their structures were elucidated as methyl gallate (1), myricitrin (2), hyperoside (3), isoquercitrin (4), quercitrin (5), spiraeoside (6), kaempferol 4'-O-β-glucopyranoside (7), chalcononaringenin 2'-O-β-glucopyranoside (8), trans-tiliroside (9), cis-tiliroside (10), and pentagalloyl-O-β-D-glucose (11), respectively. These structures of the compounds were identified on the basis of spectroscopic studies including the on-line LCNMR-MS and conventional NMR techniques. Particularly, directly coupled LC-NMR-MS afforded sufficient structural information rapidly to identify three flavonol glycosides (2 - 4) with the same molecular weight in an extract of Hamamelis japonica flowers without laborious fractionation and purification step. Cytotoxic effects of all the isolated phenolic compounds were evaluated on HCT116 human colon cancer cells, and pentagalloyl-O-β-D-glucose (11) was found to be significantly potent in inhibiting cancer cell growth.

• Korean Journal of Pharmacognosy
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• v.46 no.2
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• pp.133-139
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• 2015

Two coumarinolignans, cleomiscosins C (1) and D (2) were isolated from the heartwood of Acer mono, together with four compounds, 5-O-methyl-(E)-resveratrol-3-O-${\beta}$-D-glucopyranoside (3), 5-O-methyl-(E)-resveratrol-3-O-${\beta}$-D-apiofuranosyl-(1$\rightarrow$6)-${\beta}$-D-glucopyranoside (4), scopoletin (5), and (E)-resveratrol-3-O-${\beta}$-D-glucopyranoside (6). Of them, cleomiscosins C (1) and D (2) were applied to preparing inclusion complex molecules with ${\beta}$-cyclodextrin (${\beta}$-CD) to improve the very poor solubility in cell media. The CD complexes of 1 and 2 exhibited an enhancement of water solubility which is feasible to measure their cytotoxicity using a spectrophotometer in a cell-based assay. Anti-proliferative activity of these complex molecules was successfully estimated on HCT116 human colon cancer cells, and cleomiscosin D (2) showed anti-proliferative effects at the concentration of 1.95~31.2 ${{\mu}g}$/mL in a dose-dependent manner.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.58 no.1
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• pp.20-27
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• 2013

Proximate composition, total phenolics and total flavonoids level, DPPH radical scavenging activity, and cytotoxicity were determined in the methanol extracts of different plant parts of Youngia sonchifolia at reproductive growth stage. Crude protein and crude fat were present as the highest amount in flowers, and crude fiber in the stems and roots. The highest content of phenolics [mg ferulic acid equivalents (FAE) $kg^{-1}$ dry weight (DW)] was found in flowers (highest) and followed by leaves, stems and roots (lowest). Flavonoids [mg rutin equivalents $kg^{-1}$ DW] level, however, showed the highest in leaf extracts and lowest in root extracts. The antioxidant potential of the methanol extracts from the plants dose-dependently increased DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity (%). DPPH radical scavenging activity were highest in root extracts ($IC_{50}=1,135.6\;mg\;kg^{-1}$) and followed by leaf, stem and flower extracts. By way of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, methanol extracts of roots showed the highest anticancer activity on human cancer cell line Calu-6 for human pulmonary carcinoma ($IC_{50}=196.3\;mg\;kg^{-1}$) and HCT-116 for human colon carcinoma ($IC_{50}=623.6\;mg\;kg^{-1}$).

• Korean journal of food and cookery science
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• v.29 no.3
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• pp.241-248
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• 2013

This study was to compare the antioxidant and anti-proliferative activities of perilla (Perilla frutescens Britton) and sesame (Seasamum indicum L.) leaf extracts. The total polyphenol levels of sesame leaf ($634.7{\pm}1.2$ mg gallic acid equivalent/100 g dried leaf) were higher than those of perilla leaf ($408.7{\pm}4.6$ mg gallic acid equivalent/100 g dried leaf; p<0.001). The total flavonoid levels of sesame leaf ($166.7{\pm}17.3$ mg quercetin equivalent/100 g dried leaf) were also higher than those of perilla leaf ($108.2{\pm}3.7$ mg quercetin equivalent/100 g dried leaf; p<0.05). ABTS radical- and DPPH radical-scavenging activities of sesame leaf extracts (78.9% and 18.2%, respectively) were higher than those of perilla leaf extracts (46.0% and 9.0%, respectively; p<0.01). Both perilla and sesame leaf extracts significantly inhibited the growth of HCT116 human colon cancer cells. However, the inhibitory activities of sesame leaf extracts were more pronounced than those of perilla leaf extracts (p<0.001). These results indicate that sesame leaf extracts have higher antioxidant and anti-proliferative activities than perilla leaf extracts. More studies are needed in order to enhance the sensory value of sesame leaf and to develop sesame leaf as health/functional food ingredients.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.351-355
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• 2010

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.2
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• pp.200-207
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• 2015

Various natural products or their derivatives, mostly originating from plants, fungi, and bacteria, have been exploited as therapeutic drugs to treat various human diseases. In addition to previously explored organisms, research on natural compounds has now expanded into unexamined living organisms in order to identify novel bioactive substances. Here, we determined whether or not the larval form of the mealworm beetle Tenebrio molitor, a species of darkling beetle, contains cytotoxic substances that exclusively affect cancer cell viability. Ethanol extract and its solvent partitioned fractions, hexane and ethyl acetate fractions, showed anticancer effects against various human cancer cells derived from the prostate (PC3 and 22Rv1), cervix (HeLa), liver (PLC/PRF5, HepG2, Hep3B, and SK-HEP-1), colon (HCT116), lung (NCI-H460), breast (MDA-MB231), and ovary (SKOV3). Cell death induced by the fractions was a mix of apoptosis, necrosis, and autophagy. The hexane fraction was administered intraperitoneally to nude mice bearing a hepatocellular carcinoma SK-HEP-1 and showed inhibition of tumor growth in vivo. Therefore, we concluded that worm extracts contain cytotoxic substances, which can be enriched by proper fractionation protocols, and further separation and purification could lead to the identification of novel molecules to treat human cancers.