• Food Science and Biotechnology
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• 제16권3호
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• pp.457-462
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• 2007

Histone acetyltransferase (HAT) is a family of enzymes that regulate histone acetylation. Dysfunction of HAT plays a critical role in the development of cancer. Here we have screened the various plant extracts to find out the potent HAT inhibitors. The bellflower (Platycodon grandiflorum) root have exhibited approximately 30% of the inhibitory effects on HAT activity, especially p300 and CBP (CREB-binding protein) at the concentration of $100\;{\mu}g/mL$. The cell viability was decreased approximately 52% in LNCaP cell for 48 hr incubation. Furthermore, mRNA level of 3 androgen receptor target genes, PSA, NKX3.1, and TSC22 were decreased with bellflower root extract treatment ($100\;{\mu}g/mL$) in the presence of androgen. In ChIP assay, the acetylation of histone H3 and H4 in PSA promoter region was dramatically repressed by bellflower root treatment, but not TR target gene, Dl. Therefore, the potent HAT inhibitory effect of bellflower root led to the decreased transcription of AR target genes and prostate cancer cell growth with the repression of histone hyperacetylation.

• Fisheries and Aquatic Sciences
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• 제15권1호
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• pp.21-27
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• 2012

Ground seawater in the east area of the volcanic Jeju Island contains abundant minerals. We investigated the metabolic activity of electrodialyzed, desalted ground seawater (EDSW) from Jeju in both cultured cells and animals. The addition of EDSW to the culture medium (up to 20%, v/v) reduced the leakage of lactate dehydrogenase and increased MTT activity in CHO-IR cells. EDSW (10%) promoted insulin-induced glucose consumption in L6 muscle cells as well as the activities of the liver ethanol-metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Moreover, EDSW suppressed palmitate-induced intracellular fat accumulation in human hepatoma $HepG_2$ cells. Activities of AMP-stimulated protein kinase and acetyl CoA carboxylase, enzymes that modulate fat metabolism, were altered by EDSW in $HepG_2$ cells toward the suppression of intracellular lipid accumulation. EDSW also suppressed hepatic fat accumulation induced by a high-fat diet in mice. Taken together, EDSW showed beneficial metabolic effects, including the enhancement of ethanol metabolism and insulin-induced glucose consumption, and the suppression of intrahepatic fat accumulation.

• Biomolecules & Therapeutics
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• 제32권2호
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• pp.214-223
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• 2024

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

• Reproductive and Developmental Biology
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• 제34권3호
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• pp.143-151
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• 2010

Pluripotency of human embryonic stem cell (hESC) is one of the most valuable ability of hESCs for applying cell therapy field, but also showing side effect, for example teratoma formation. When transplant multipotent stem cell, such as mesnchymal stem cell (MSC) which retains similar differentiation ability, they do not form teratoma in vivo, but there exist limitation of cellular source supply. Accordingly, differentiation of hESC into MSC will be promising cellular source with strong points of both hESC and MSC line. In this study, we described the derivation of MSC like cell population from feeder free cultured hESC (hESC-MSC) using direct differentiation system. Cells population, hESC-MSC and bone marrow derived MSC (BM-MSC) retained similar characteristics in vitro, such as morphology, MSC specific marker expression and differentiation capacity. At the point of differentiation of both cell populations, differentiation rate was slower in hESC-MSC than BM-MSC. As these reason, to verify differentially expressed molecular condition of both cell population which bring out different differentiation rate, we compare the molecular condition of hESC-MSC and BM-MSC using 2-D proteomic analysis tool. In the proteomic analysis, we identified 49 differentially expressed proteins in hESC-MSC and BM-MSC, and they involved in different biological process such as positive regulation of molecular function, biological process, cellular metabolic process, nitrogen compound metabolic process, macromolecule metabolic process, metabolic process, molecular function, and positive regulation of molecular function and regulation of ubiquitin protein ligase activity during mitotic cell cycle, cellular response to stress, and RNA localization. As the related function of differentially expressed proteins, we sought to these proteins were key regulators which contribute to their differentiation rate, developmental process and cell proliferation. Our results suggest that the expressions of these proteins between the hESC-MSC and BM-MSC, could give to us further evidence for hESC differentiation into the mesenchymal stem cell is associated with a differentiation factor. As the initial step to understand fundamental difference of hESC-MSC and BM-MSC, we sought to investigate different protein expression profile. And the grafting of hESC differentiation into MSC and their comparative proteomic analysis will be positively contribute to cell therapy without cellular source limitation, also with exact background of their molecular condition.

• 대한수의학회지
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• 제60권2호
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• pp.79-83
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• 2020

Fenbendazole (FBZ) is a benzimidazole anthelmintic that has been widely used in treatments for gastrointestinal parasites including pinworms and roundworms in animals. Recently, some studies demonstrated that FBZ has anti-cancer effects related to disruption of microtubule polymerization. In this study, we investigated whether FBZ has anti-cancer activity in HL-60 cells, a human leukemia cell line, and assessed its relationship with the production of reactive oxygen species (ROS). FBZ treatment at 0.25-1 μM significantly decreased the metabolic activity of HL-60 cells. The mitochondrial membrane potential of FBZ-treated HL-60 cells decreased in a concentration-dependent manner. Apoptosis analysis using annexin V-FITC/propidium iodide staining demonstrated that 1 μM FBZ increased the percentages of cells in apoptosis and necrosis. In addition, Hoechst 33342 staining showed the presence of broken nuclei in HL-60 cells treated with 0.5 and 1 μM FBZ. To investigate the anti-cancer mechanism of FBZ, HL-60 cells were treated with FBZ in the absence or presence of N-acetyl cysteine (NAC), an inhibitor of ROS production. NAC significantly recovered the decreased metabolic activity of HL-60 induced by 0.5 and 1 μM FBZ treatments. This study provides evidence that FBZ has anti-cancer activity in HL-60 cells provided, in part, via ROS production.

• Journal of Biosystems Engineering
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• 제39권3호
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• pp.235-243
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• 2014

Purpose: The aim of this study was to prepare and evaluate a natural material extracted from germinated brown rice (GBR). Herein, we evaluated whether the natural material could positively activate the biological effects seen during bone formation, including enhancement of metabolic activity, osteogenesis, and the expression of vascular endothelial growth factor (VEGF), one of the growth factors in human osteoblast-like cells. Methods: The natural material was created by a hot water extraction process after being soaked for 2~3 days in tap water and dried at $50^{\circ}C$. The material was characterized using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transformed infrared (FTIR) spectroscopy. The biological behaviors of the material were also investigated; we performed tests to assess cell cytotoxicity, metabolic activity, osteogenic markers related to bone formation, and VEGF. Results: The EDX, XRD, and FTIR results for the natural material indicated the presence of organic compounds. The natural material caused positive increases in cell metabolic activity and mineralized bone formation without cytotoxicity. The protein levels in the extract for the $6.25{\mu}g/mL$, $12.25{\mu}g/mL$, $25{\mu}g/mL$, $50{\mu}g/mL$, and $100{\mu}g/mL$ groups were significantly different from that for the control. Conclusions: The GBR-based natural material was easy to prepare and had characteristics of a potential biomaterial. The biocompatibility of this natural material was evaluated using in vitro techniques; our findings indicate that this novel material is promising for agricultural and biological applications.

• Applied Microscopy
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• 제43권3호
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• pp.117-121
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• 2013

Mitochondrion is an important intracellular organelle controlling energy production essential for cell survival. In addition, it is closely related to cellular apoptosis and necrosis. Linear, branched, circular, and ball-shaped mitochondria have been reported. Recent research suggests that mitochondrial morphology may reflect functional status of the cell. In this study, we investigated the density and ratio of the each morphological categories of mitochondria in a few normal cultured cells; astrocyte, HeLa and COS7 cells, of which metabolic activities are different, with high voltage electron microscopy. The absolute number and relative number per unit area of mitochondria was largest in astrocyte. But, the proportion of different mitochondrial shape was similar among cells. These results shows the numerical profiles but not morphological profiles of mitochondria are related to the metabolic activity of each cell line.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4241-4244
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• 2012

The lung adenocarcinoma is considered more aggressive than other types of non-small cell lung cancer. As metabolites of tryptophan degradation along the kynurenine pathway, including kynurenic acid, have been shown to induce immunosuppression and facilitate escape of tumor cells from immune surveillance, a hypothesis was set up that differences in biological behavior between types of lung cancer may be associated with altered activity of the kynurenine metabolic pathway. The aim of the study was to determine kynurenic acid levels in the serum of patients with bronchial adenocarcinoma for comparison with other types of non-small cell lung cancer. A total of 227 patients with non-small cell lung cancer were enrolled in the study, including 71 with adenocarcinoma and 96 with squamous cell carcinoma. Serum kynurenic acid concentration was determined with use of high performance liquid chromatography and fluorometry. The level of kynurenic acid in the serum of patients with adenocarcinoma was significantly higher than in those with squamous cell lung cancer ($107.1{\pm}62.8$ pmol/ml; 95%CI: 92.4 to 132.3 pmol/ml versus $82.1{\pm}47.6$ pmol/ml; 95%CI: 78.5 to 91.2 pmol/ml, respectively; p = 0.027). Differences between other histological types of lung cancer were insignificant. We conclude that increased activity of kynurenine metabolic pathway manifested by elevated serum kynurenic acid level may be one of the factors associated with clinically distinct biological behavior of adenocarcinoma, in particular high invasiveness and rapid progression.

• Nutrition Research and Practice
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• 제5권3호
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• pp.205-213
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• 2011

Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC- $1{\alpha}$, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, ($5\;{\mu}mol{\cdot}kg$ body $wt^{-1}{\cdot}day^{-1}$) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-la, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.

• Ocean and Polar Research
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• 제24권1호
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• pp.47-53
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• 2002

To evaluate the effect of reed population on the distribution and activities of microorganisms, vertical distribution of heterotrophic bacteria, degradation rate of cellulose, extracellular aminopeptidase activity (APA) and metabolic diversity based on GN2 Microlog plate were measured at two salt marsh stations in Hogok-ri, Namyang Bay, west coast of Korea. The number of heterotrophic bacteria at station 1 (reed population inhabited area) showed 2 to 6 times higher than that of station 2 (exposed area) with exception in the surface layer. Cellulose degradation rates in station 1 showed more than 50%. month-I and higher than that of station 2 (10.2 to 38.4%. $month^{-1}$). Yet the APA at two stations did not show difference except surface layer and suggested that APA might not be a significant factor in degrading marsh plant debris. Lipid class compounds, cell wall polymers and L-alanine were widely used by microorganisms. The number and activities of bacterial populations especially concerned in plant debris degradation seemed to be stimulated by the reed communities.