• Nutrition Research and Practice
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• v.9 no.6
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• pp.628-636
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• 2015

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5343-5348
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• 2015

Promoter hypermethylation of the runt-related transcription factor 3 (RUNX3) gene is associated with increased risk of hepatocellular carcinoma (HCC). Oxidative stress plays a vital role in both carcinogenesis and progression of HCC. However, whether oxidative stress and RUNX3 hypermethylation in HCC have a cause-and-effect relationship is not known. In this study, plasma protein carbonyl and total antioxidant capacity (TAC) in patients with hepatitis B virus (HBV)-associated HCC (n=60) and age-matched healthy subjects (n=80) was determined. RUNX3 methylation in peripheral blood mononuclear cells (PBMC) of subjects was measured by methylation-specific PCR. Effect of reactive oxygen species (ROS) on induction of RUNX3 hypermethylation in HCC cells was investigated. Plasma protein carbonyl content was significantly higher, whereas plasma TAC was significantly lower, in HCC patients than healthy controls. Based on logistic regression, increased plasma protein carbonyl and decreased plasma TAC were independently associated with increased risk for HCC. PBMC RUNX3 methylation in the patient group was significantly greater than in the healthy group. RUNX3 methylation in hydrogen peroxide ($H_2O_2$)-treated HepG2 cells was significantly higher than in untreated control cells. In conclusion, increase in oxidative stress in Thai patients with HBV-associated HCC was demonstrated. This oxidative increment was independently associated with an increased risk for HCC development. RUNX3 in PBMC was found to be hypermethylated in the HCC patients. In vitro, RUNX3 hypermethylation was experimentally induced by $H_2O_2$. Our findings suggest that oxidative stress is a cause of RUNX3 promoter hypermethylation in HCC cells.

• Applied Biological Chemistry
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• v.50 no.4
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• pp.358-361
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• 2007

The heartwoods of Rhus verniciflua was extracted with $H_2O$ and the concentrated extract was partitioned with $CHCl_3$, EtOAc, n-BuOH and $H_2O$, successively. From the EtOAc and n-BuOH fractions, four compounds were isolated through the repeated silica gel, ODS and Sephadex LH-20 column chromatographies. They were determined as sinapyl aldehyde (1), 2,4-dihydroxybenzaldehyde (2), 2,4-dihydroxybenzoic acid (3) and 2,4-dihydroxyphenylglyoxylic acid (4) on the basis of spectroscopic data, respectively. Among the isolated compounds, sinapyl aldehyde $(34.7{\pm}0.6%)$ and 2,4-dihydroxyphenylglyoxylic acid $(43.8{\pm}0.9%)$ showed the strong antioxidative activity than artificial antioxidant BHT $(14.4{\pm}0.3%)$ in DPPH radical scavenging activity.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.893-900
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• 2004

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

• Korean Journal of Food Science and Technology
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• v.31 no.4
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• pp.1065-1070
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• 1999

This study was performed to determine the antimutagenic and cytotoxic effect of Aster scaber root ethanol extract on Salmonella typhymurium TA98, TA100 and cancer cell lines using Ames test and cytotoxicity assay, respectively. Cancer cell lines include chronic myelogenous leukemia(K562), human gastric carcinoma(KATOIII), human hepatocellular carcinoma(Hep3B) and human breast adenocarcinoma(MCF-7). Futher fractionations with hexane, chloroform, ethyl acetate, butanol and water from ethanol extract of Aster scaber root were performed to obtain effective fraction. Ethanol extract and ethyl acetate fraction showed 79% and 82% inhibitory effect on the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) against TA100, while 48% and 60% inhibition was observed on the mutagenesis induced by 4-nitroquinoline-l-oxide(4NQO) against TA98. In the meanwhile, ethyl acetate fraction showed 78% and 85% inhibitory effect on the mutagenesis induced by benzo(${\alpha}$)pyrene[B(${\alpha}$)P] against TA98 and TA100, respectively, while 83% inhibition was observed on the mutagenesis induced by 3-amino-l,4-dimethyl-5H-pyrido(4,3-b) indole(Trp-P-1) against TA98. Ethyl acetate fraction (0.125 mg/ml) showed the strongest cytotoxic effect against K562, KATOIII, Hep3B and MCF-7 at the same concentration compared to those of other fractions. Ethanol extract and water fraction showed the least inhibitory effect.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.115-123
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• 2006

Objective: To investigate new signal transduction cascade through integrin, FAK and ERK in the suppressed cell proliferation by GnRH-I and -II. Method: Human endometrial cancer cells (HEC1A) were cultured under the following condition: DMEM/F12 (10% FBS). GnRH-I and -II were treated time (0, 5, 10, 15, 20, 30 min; 100 nM) and dose (10 nM or 100 nM; 20 min) dependent manner according to experimental purposes. Cell proliferation was measured using [$^3H$] thymidine incorporation assay. Immunoblotting was utilized to detect proteins. Results: GnRH-I and -II inhibited proliferation of HEC1A cells and induced expression of integrin ${\beta}3$. Phosphorylation of FAK and ERK were induced by GnRH-I and -II. Conclusion: GnRH inhibited cell proliferation via the expression of integrin and FAK, ERK phosphorylation.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.69-69
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• 2003

Human CD99 is a ubiquitous 32-kDa transmembrane protein encoded by the mic2 gene. The major cellular functions of CD99 protein are related to homotypic cell adhension, apoptosis, vesicular protein transport, and differentiation of thymocytes or T cells. Recently it has been reported that expression of a splice variant of CD99 transmembrane protein (Type I and Type II) increases invasive ability of human breast cancer cells. To understand structural basis for cellular functions of CD99 (Type I), we have initiated studies on hCD99$^{TMcytoI}$ and hCD99$^{cytoI}$ using circular dichroism (CD) and multi-dimensional NMR spectroscopy. CD spectrum of hCD99$^{TMcytoI}$ in the presence of 200mM DPC and CHAPS displayed an existence $\alpha$-helical conformation. The solution structure of hCD99$^{cytoI}$ determined by NMR is composed of one N-terminal $\alpha$-helix, $\alpha$A, two C-terminal short $\alpha$-helix segments, $\alpha$B and $\alpha$C. While $\alpha$A and $\alpha$B are connected by the long flexible loop, $\alpha$B and $\alpha$C connected by type III$\beta$-turn. Although it has been rarely figured out the correlation between structure and functional mechanism of hCD99$^{TMcytoI}$ and hCD99$^{cytoI}$, there is possibility of dimerization or oligomerization. In addition, the feasible mechanism of hCD99$^{cytoI}$ is that it could have intramolecular interaction between the N- and C- terminal domain through large flexible AB loop.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.186-190
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• 2012

Nuclear factor-${\kappa}B$ (NF-${\kappa}B$) has been considered as one of the major targets for therapeutic agents of diverse human diseases. In the previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) and chroman-2-carboxylic acid N-(4-chlorophenyl)amide were identified as good inhibitors of NF-${\kappa}B$ activation. In this continuous study, we describe the synthesis and NF-${\kappa}B$ inhibitory activities of chroman derivatives containing N-heteroaryl groups for exploration of SAR (structure-activity relationship). In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3).

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.90-95
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• 2006

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1238-1254
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• 2023

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m² or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers.