• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5181-5185
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• 2015

Background: CCAT1 has been reported to be linked with pathogenesis of malignancies including colon cancer and gastric cancer. However, the regulatory effect of CCAT1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this research was to identify any role of CCAT1 in the progression of HCC. Materials and Methods: Real time-PCR was performed to test the relative expression of CCAT1 in HCC tissues. A computation screen of CCAT1 promoter was conducted to search for transcription-factor-binding sites. The association of c-Myc with CCAT1 promoter in vivo was tested by Pearson correlation analysis and chromatin immunoprecipitation assay. Additionally, Kaplan-Meier analysis and Cox proportional hazards analyses were performed. Results: c-Myc directly binds to the E-box element in the promoter region of CCAT, and when ectopically expressed increases promoter activity and expression of CCAT1. Moreover, Kaplan-Meier analysis demonstrated that the patients with low expression of CCAT1 demonstrated better overall and relapse-free survival compared with the high expression group. Cox proportional hazards analyses showed that CCAT1 expression was an independent prognostic factor for HCC patients. Conclusions: The findings demonstrated CCAT1, acting as a potential biomarker in predicting the prognosis of HCC, is regulated by c-Myc.

• Molecules and Cells
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• v.39 no.4
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• pp.330-336
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• 2016

Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cance-rassociated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Reintroduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

• Journal of Life Science
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• v.24 no.11
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• pp.1224-1230
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• 2014

The red radish (Raphanus sativus L.; RR) sprout is a plant of the cruciferous family. In this study, we elucidated the effect of the water extract of RR sprout (RRSE) against ${\alpha}$-amylase, ${\alpha}$-glucosidase, and pancreatic lipase enzyme activity and adipogenesis in 3T3-L1 preadipocytes. ${\alpha}$-amylase, ${\alpha}$-glucosidase, and pancreatic lipase enzyme activity was inhibited in a concentration-dependent manner by RRSE treatment. RSSE also abolished adipocyte differentiation and lipid and triglyceride accumulation without cytotoxicity in 3T3-L1 adipocytes. In addition, RRSE modulated the expression of the proteins related to adipogenic transcription factors: peroxisome proliferator-activated receptor (PPAR)${\gamma}$, sterol regulatory element-binding protein 1 (SREBP-1), and CCAT/enhancer binding protein (C/EBP)${\alpha}$. RRSE also suppressed expression of the proteins responsible for lipid synthesis, transport, and storage: adiponectin, fatty acid synthesis (FAS), perilipin, and fatty acid bind protein-4 (FABP4). This study showed that RRS treatment has the potential to inhibit obesity by controlling the expression of adipogenic transcription factors and adipogenic proteins.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.1
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• pp.24-29
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• 2020

In this study, we investigated the inhibition effects of mixtures of Atractylodes macrocephala (AM) and Amomum villosum (AV) water extracts on adipocyte differentiation. Treatment with mixtures of AM and AV extracts in a ratio of 3:1 for 24 and 48 hours did not show any cytotoxicity in OP9 cells. Mixtures of AM(3) and AV(1) extracts inhibited adipocyte differentiation, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation. It also inhibited the expression of lipoprotein lipase (LPL), adipocyte protein 2 (aP2), which are PPARγ-target genes in adipocyte. We also checked the inhibition effects on cell proliferation during the early stage of differentiation by treatment with mixtures of AM(3) and AV(1) extracts. It markedly inhibited adipocyte proliferation after 48 hours, and also the phosphorylation of ERK1/2 and Akt after 10 min or 3 hour. These results identify a possible mechanism of action of mixtures of AM(3) and AV(1) extracts, suggesting that the mixtures of AM(3) and AV(1) extracts-induced inhibition of ERK and Akt phosphorylation suppresses adipogenesis by inhibiting other signaling cascades that include PPARγ and C/EBPα during the process of OP9 adipocyte differentiation.

• The Korea Journal of Herbology
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• v.28 no.1
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• pp.23-31
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• 2013

Objectives : The purpose of this study was to determine the anti-obesity effect and molecular mechanism of YY312, a herbal extract composed of Imperatae Rhizoma, Citri Unshius Pericarpium Immaturus, and Evodiae Fructus, on a high-fat diet-induced animal model and on 3T3-L1 cells. Methods : C57BL/6 mice were fed for 6 weeks with a normal diet or a high-fat diet (HFD). Then they orally administered daily with 300 mg/kg YY312 for next 10 weeks. Body weight and food consumption were recorded weekly and daily, respectively. Tissue weights, serum lipid, and glucose levels were analyzed at the end of the study. Additionally, the effects of YY312 on adipocyte differentiation in 3T3-L1 cells were examined. After differentiating 3T3-L1 cells were treated with YY312, Oil-red O staining, RT-PCR, and Western blotting were performed for lipid accumulation, mRNA expression of adipogenesis gene, and AMP-activated protein kinase (AMPK) phosphorylation, respectively. Results : YY312-administered mice showed a significant reduction of body weights and abdominal adipose tissue weights. YY312 also reduced the serum levels of triglycerides and total cholesterol, compared with the HFD group. Treatment with YY312 inhibited lipid accumulation and blocked expression of adipogenic transcription factors and lipogenesis genes, including peroxisome proliferator-activated receptor ${\gamma}$, CCAT/enhancer binding protein ${\alpha}$ and fatty acid synthase. YY312 increased AMPK phosphorylation in 3T3-L1 adipocytes. Conclusions : This study showed that herbal extract YY312 has an anti-obesity effect in vitro and in vivo. Thus, YY312 could be developed as a supplement for reduction of body weight gain induced by an HFD.

• Herbal Formula Science
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• v.25 no.4
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.1
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• pp.26-32
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• 2013

Boesenbergia pandurata (Roxb.) Schltr. has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of Boesenbergia pandurata extract (BPE) in a high-fat diet (HFD)-induced obese mice model. C57BL/6J mice were fed with either the high-fat diet or a 0.5% BPE-supplemented HFD for 8 weeks. The BPE-containing HFD significantly reduced body weight gain and the accumulation of visceral fat mass in mice model without altering the amount of food intake. Moreover, mice fed with BPE-containing HFD had lower concentrations of lipids in their blood, lower hepatic lipid accumulation, and lower serum leptin levels compared with the HFD-fed mice. RT-PCR analysis showed that the expression levels of peroxisome proliferators-activated receptor ${\gamma}2$ ($PPAR{\gamma}2$) and CCAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$) genes in the epididymal fat tissue of mice fed the BPE-containing HFD increased 1.16- and 1.30-fold, respectively, compared to mice fed HFD only. In conclusion, BPE attenuated visceral fat accumulation and improved dyslipidemia in a mice model with HFD-induced obesity.

• Food Science of Animal Resources
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• v.33 no.3
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• pp.411-416
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• 2013

This study aimed to examine the mechanisms underlying the effects of Garcinia cambogia extract on the adipogenic differentiation of 3T3-L1 cells and long-chain saturated fatty acid-induced lipotoxicity of HepG2 cells. 3T3-L1 preadipocytes, mouse embryonic fibroblast-adipose like cell line, were treated with MDI solution (0.5 mM IBMX, 1 ${\mu}M$ dexamethasone, 10 ${\mu}g/mL$ insulin) to generate a cellular model of adipocyte differentiation. Using this cellular model, the anti-obesity effect of Garcinia cambogia extract was evaluated. MDI-induced lipid accumulation and expression of adipogenesis-related genes were detected by Oil red O staining, Nile Red staining, and Western blot analysis. Effects Garcinia cambogia extract on palmitate-induced lipotoxicity was also analyzed by MTT assay, LDH release, and DAPI staining in HepG2 cells. Garcinia cambogia extract significantly suppressed the adipogenic differentiation of preadipocytes and intracellular lipid accumulation in the differentiating adipocytes. Garcinia cambogia extract also markedly inhibited the expression of peroxisome proliferator- activated receptor ${\gamma}2$ ($PPAR{\gamma}2$), CCAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), and adipocyte protein aP2 (aP2). In addition, Garcinia cambogia extract significantly attenuated palmitate-induced lipotoxicity in HepG2 cells. Palmitateinduced cellular damage and reactive aldehydes were also significantly reduced in the presence of Garcinia cambogia extract. These findings suggest that the Garcinia cambogia extract inhibits the adipogenic differentiation of 3T3-L1 preadipocytes, probably by regulating the expression of multiple genes associated with adipogenesis such as $PPAR{\gamma}2$, $C/EBP{\alpha}$, aP2, and thereby modulating fatty acid-induced lipotoxicity to reduce cellular injury in hepatocytes.