• Proceedings of the PSK Conference
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• 2002.10a
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• pp.312.3-313
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• 2002

Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

• Food Science of Animal Resources
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• v.27 no.4
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• pp.531-537
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• 2007

Small amounts of trans fatty acids exist naturally in beef and dairy foods. Also, they can be produced in the process of partial hydrogenation to manufacture shortning or margarine. They can provide a better palatability and shelf life. According to the recently studies, trans fatty acids can raise health risk such as heart diseases and coronary artery diseases. They can also increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) cholesterol in the blood plasma, therefore increasing the risk of atherosclerosis and diabetes. The aim of this study was to determine total lipids and trans fatty acids (TFAs) content in processed foods and meat products. The analysis of trans fatty acids was performed in 28 samples of donuts, 18 samples of bakeries, 4 samples of frozen doughs, 2 samples of popcorns, and 4 samples of meat products (ham, sausage, nuget, and bacon). Total lipids in processed foods and meat products were extracted by chloroform-Methanol method and acid digestion, respectively. They were analyzed by gas chromatography using a SP-2560 column and flame ionization detector. The amounts of TFAs per 100 g of foods were 0-3.3% (0.74% on average) in donuts, 0.2-5.8% (1.18% on average) in bakeries, 0.2-6.3% (1.93% on average) in frozen doughs, and 0-5.8% in popcorns. Meat products such as ham, sausage, and nuget analyzed 0.1% of TFAs, respectively and trans fatty acids in bacon were not detected. As a result, the distribution of TFAs in processed foods was widely ranged from O% to 6.3% according to manufacturers and types of products, whereas the content of TFAs in meat products ranged from 0% to 0.1%.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.134-140
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• 2015

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA increases $GSK3{\beta}$ expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of $GSK3{\beta}$ and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.336-342
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• 2008

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.11-16
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• 1988

Various Benzylacyclouridine (BAU, HM-BAU, suc-BAU, BBAU, HMBBAU, suc-BBAU, and BBBAU) developed as specifc inhibitors of uridine phosphorylase (UrdPase), inhibit transport (zero-trans influx) of ridine (Urd) in human erythrocytes. The inhibition pattern of these compounds is competitive, though suc-BBAU and BBBAU show a slight noncompetivieness. The order of potency as an inhibitor of the nucleoside transport system is BBAU ${\sim}$ HM-BBAU ${\sim}$ suc-BBAU > BBBAU > BAU ${\sim}$ suc-BAU ${\sim}$ HM-BAU ($K_1$ values of 19, 23, 38, 112, 124, 174 and 176 ${\mu}M$, respectively). These data indicate that there is a differnece in potency of Urd transport inhibition between the analogs of BAU and BBAU. Further, the potency correlates with the hydrophobicity of the compound, but it has a limit in the size of $C_5$ substitution. Abbreviation: BAU (5-benzylacyclouridine), 5-benzyl-1-(2'-hydroxyethoxymethyl) uracil; HM-BAU (3'-hydroxymethyl-BAU), 5-benzyl-1- [(1',3'-dihydroxy-2-propoxy) methyl]uracil; suc-BAU, 3'-succinyl-BAU; BBAU (benzyloxybenzylacyclouridine), 5-( m-benzyloxybenByl)-1-(2'-hydroxyethoxymethyl)uracil; HM-BBAU (3'-hydroxymethyl-BBAU), 5-(m-benzyloxybenzyl)-1- [(1'3'-dihyd.oxy-2-p.epoxy)methyll u.acil; suc-BAU, 3'-succinyl-BBAU; BBBAU, 5- f 3-(4-benzyloxyben-Eyl)benzyll -1-(2'-hydroxyethoxymethyl)uracil; Urdpase, uridine phosphorylase; Urd, Uridine; Fd-Urd, 5-fluoro-2'-deoxyuridine; AcThd, aoyclothyrnidine; AcUrd, acyclouridine; dThd, thymidine; NBMPR, nitrobenzylthioisone; FUra, 5-fluorouracil.

• 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 Photoscience
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• v.9 no.2
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• pp.518-520
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• 2002

Photodynamic therapy (PDT) is a treatment modality based on photochemical reaction and the resultant cytotoxic reactive oxygen species. The platelet thrombus formation leading to stasis observed in vivo during PDT is called vascular shut down (VSD) effect. To investigate the mechanism of the VSD effect, we observed Human Umblical Vein Endothelial Cell (HUVEC) injury induced by photochemical reaction. We observed cell retraction and blebbing after PDT. It seems that the injury was not fetal and only morphological change. Then, the cytoplasm was stained by Calcein-AM and subendothelial area was evaluated from fluorescence microscopy. The rate of subendothelial area after PDT increased significantly. Second, we investigated interaction between neutrophils and HUVEC. Human promyelocytic leukemia cells (HL-60) were differentiated into neutrophil by incubation with all-trans retinoic acid. Calcein-AM labeled neutrophil adhesion to HUVEC was evaluated from fluorescence microscopy. PDT-induced neutrophil adhesion to HUVEC depended more on the exposure of subendothlial area than on neutrophil activation. This result suggests that there is a certain interaction between neutrophil and HUVEC during PDT.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.23 no.3
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• pp.9-23
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• 1997

Retinoids are essential regulators of spithelial cell growth and celluar differentiation. They are also known to be effective in photoaging. It was reported that topical application of retinoic acid improves facial wrinkle carsed by collagen synthesis reduction in photodamaged skin. Collagen synthesis by retinoic acid may contribute to the wrinkle effacement. Since celluar retinoic acid binding protein II is slsctively induced in human skin and dermal fibroblasts in vitro by retinoic acid, this response can be used to mesure retinoids potency and activity. In order to know the activity of retinoids and their relations with collagen synthesis, we treated dermal fibroblasts with retinoids for 48 hours at 10-6-10-7M and measured CRABPII mRNA level by quantitative Nortern blotting. We also measured the rate of collagen systhesis by retinoids using 3-dimensional dermal equivalent. CRABPII mRNA level was increased 3-fold by retinoic acid, 2.1-fold by retinol and 1.4-fold by retinaldehyde. Collagen systhesis was increased 34% by all-trans retinioc acid, 26% by retinol, 17% by retinaldehyde and 7% by retinyl palmitate. From the above results, retinoids were found to be a potent indecers of CRABPII mRNA and collagen synthesis. Though retinoic acid was the most effective, its use has been restricted because of the side effects. Instead, retinol can be a best candidate in cosmetics for the treatment of photodamaged skin in terms of efficacy and safety.

• Natural Product Sciences
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• v.10 no.6
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• pp.335-340
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• 2004

The chromatographic separation of the MeOH extract of the aerial parts from Aster hispidus (Compositae) led to the isolation of eight compounds. Their structures were established by spectroscopic methods to be ${\beta}-amyrin$ (1), oleanolic acid (2), (2R)-1, 2-O-(9Z, 12Z, $15Z-dioctadecatrienoyl)-3-O-{\beta}-D-galactopyranosyl\;glycerol$ (3), trans-phytol (4), 9, 12, 15-octadecatrienoic acid (5), kaempferol (6), 3,5-dicaffeoyl quinic acid (7), 3,4-dicaffeoyl quinic acid (8) and kaempferol-3-O-rutinoside (9). Compounds 1, $3{\sim}6$ and 9 showed non-specific moderate cytotoxicity against five human tumor cell lines $(5.44{\sim}23.51\;{\mu}g/ml)$. The other compounds were of marginal activity against tested five human cancer cell lines $(9.05{\sim}>30.0\;{\mu}g/ml)$.

• Archives of Pharmacal Research
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• v.27 no.8
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• pp.845-849
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• 2004

Many studies have focused on the anticarcinogenic, antimutagenic or chemopreventive activi-ties of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) which is a major pungent ingredient in red pepper. We have previously shown that capsaicin selectively induces apoptosis in H-ras-transformed MCF10A human breast epithelial cells but not in their normal cell counter-parts (Int. J. Cancer, 103, 475-482,2003). In this study, we investigated the possible roles of reactive oxygen species (ROS) and Rac1 in capsaicin-induced apoptosis of H-ras MCF10A cells. Selective induction of ROS generation by capsaicin treatment was observed only in H-ras MCF10A cells. Pretreatment of H-ras MCF10A cells with an antioxidant N-acetylcysteine(NAC) significantly reversed capsaicin-induced growth inhibition, suggesting that ROS may mediate the apoptosis of H-ras-transformed cells induced by capsaicin. Rac1 was prominently activated by H-ras in MCF10A cells. Based on the studies using a wild type Rac1 and a domi-nant negative Rac1 constructs, we propose that Rac1 activity is critical for inhibitory effect of capsaicin on growth of H-ras-transformed MCF10A cells possibly through ROS generation.