• BMB Reports
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• v.51 no.10
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• pp.532-537
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• 2018

Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because $PGE_2$ functions by signaling through $PGE_2$ receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and $PGE_2$ production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• BMB Reports
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• v.44 no.7
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• pp.484-489
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• 2011

Annexin-1 (ANX1) is an anti-inflammatory protein as well as an important modulator in inflammation. However, the precise action of ANX1 remains unclear. To elucidate the protective effects of ANX1 on lipopolysaccharide (LPS)-induced murine macrophage Raw 264.7 cells, we constructed a cell-permeable Tat-ANX1 protein. The transduced Tat-ANX1 protein markedly inhibited the expression of cyclooxygenase-2, production of prostaglandin $E_2$, and generation of pro-inflammatory cytokines in the cells. Furthermore, transduced Tat-ANX1 protein caused a significant reduction in the activation of nuclear factor-kappa B (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK). The results indicate that Tat-ANX1 inhibits the production of inflammatory response cytokines and enzymes by blocking NF-${\kappa}B$ and MAPK. Therefore, Tat-ANX1 protein may be useful as a therapeutic agent against various inflammatory diseases.

• BMB Reports
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• v.45 no.12
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• pp.742-747
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• 2012

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

• BMB Reports
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• v.48 no.11
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• pp.618-623
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• 2015

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI.

• Journal of Life Science
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• v.30 no.10
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• pp.835-843
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• 2020

Obesity, the world's leading metabolic disease, is a serious health problem in both industrialized and developing countries. Natural substances are of great interest in preventative medicine, especially in the field of metabolic syndromes-from insulin resistance to obesity and diabetes. In the present study, we investigated the effect of A. pullulans SM-2001 Extract (Polycan^®) on the adipocyte differentiation of 3T3-L1 preadipocytes and the anti-obesity effect of 3T3-L1 adipocytes. Although β-glucan has been found to have health benefits in the regulation of the immune system and blood cholesterol levels, its role in obesity has not been fully investigated. Polycan^® suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity without affecting cell viability in 3T3-L1 preadipocytes and adipocytes. Polycan^® also inhibited cellular lipid accumulation through down-regulation of transcription factors, such as PPARγ and C/EBPα, and induced dose-dependent phosphorylation of AMP-activated protein kinase (AMPK)-a cellular energy sensor-while the total AMPK protein content remained unchanged. Taken together, this shows that the activation of AMPK by Polycan^® in adipocytes plays a critical role in Polycan^®-induced inhibition of adipocyte differentiation. Our results show that Polycan^® has an anti-obesity action in vitro, suggesting a potential novel preventative agent for obesity and other metabolic diseases.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.440-451
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• 1997

This study was designed to prospect the $^{111}In$-labelled paclitaxel as tumor imaging agent. In order to provide a taxol molecule with a functional group which is able to chelate In-111, taxol-DTPA conjugate and 2'-hemisuccinyltaxol were synthesized by esterification of taxol at C-2'on C-13 carbon with DTPA anhydride and succinic anhydride, respectively. Synthesis yield of the taxol derivatives was 34% for taxol-DTPA and 80% for 2'-hemisuccinyltaxol. Cytotoxicity of the taxol derivatives were measured by MTT method toward cell lines HT29, B16, P388, and CT26. The cytotoxic activities of the taxol derivatives were maintained, although less active than taxol. Radiolabelling of the taxol derivatives were proceeded directly with $^{111}InCl_3$ or indirectly with $^{111}In$-citrate(ligand-exchange method). The ligand-exchange method was not suitable because some precipitates appeared during the reaction. On the contrary, by direct radiolabelling method, we were able to obtain taxol-DTPA-$^{111}In$ in 100% radiochemical yield. However, 2'-hemisuccinyltaxol was not labelled by both methods. Yield and radiochemical purity of the radiolabelled com-pound were determined by HPLC, paper chromatography and instant thin layer chromatography. Taxol-DTPA-$^{111}In$ was characterized to be hydrophilic by lipophilicity test, and nearly non-adhesive to HT29, B16, P388, and CT26 by cell binding affinity test. Binding affinity of the taxol-DTPA-$^{111}In$ complex to serum proteins was also examined by protein precipitation with 30% trichloroacetic acid. The results showed that 30% of the taxol-DTPA-$^{111}In$ complex binds with serum proteins.

• Korean Journal of Ecology and Environment
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• v.38 no.3 s.113
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• pp.313-321
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• 2005

Based on the result that biological control agent (BCA) increased the dissolved microcystin-LR in a field experiment to control the cyanobacterial bloom (Kim etal., 2005), a laboratory experiment was used to evaluate the effects of dissolved microcystin-LR (MCLR) with different concentrations on abundance, dominance, diversity of phytoplankton community, concentration of chlorophyll a and microcystin concentration in replicated microcosms. The treatments in this laboratory experiment comprised different concentrations of T1 (natural MCLR concentration), T10 (ten times to natural MCLR concentration), and T100 (one hundred times to natural MCLR concentration). MCLR treatment of exclusively Stephanodiscus hantzschii-dominated community in Chonho bridge hardly changed in algal species, but abundance. In Kildong pond, Aulacoseira and Dinobryonrich community was replaced by green algae Scenedesmus-rich community especially in T100 experiment. However, in Yangsoori-Ryukgakji Pond having the highest concentration of initial MCLR, Microcystis aeruginosa was decreased in abundance. Therefore, the treatment of BCA to control M. aeruginosa severely changed the Phytoplankton community in term of algal species, abundance (chlorophyll a) and dissolved microcystin-LR via a high release of MCLR.

• Journal of Life Science
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• v.14 no.5
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• pp.800-808
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• 2004

Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including antioxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-$X_L$levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-l and proliferating cell nuclear antigen protein, and inhibited the expression of $\beta$-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2001.11a
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• pp.43-56
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• 2001

Colostrum contains various kinds of cytokines including TGF-${\beta}$ which is known to be multifunctional in immune response and act as an anti-inflammatory agent. First, we measured the amount of TGF-${\beta}$ in bovine and human colostrum. Expression pattern of TGF-${\beta}$ isotypes was dramatically different between human and bovine colostrial samples. Bovine colostrum collected on day 1 post-delivery retained $41.79{\pm}16.96ng/ml$ of TGF-${\beta}$ 1 and $108.4{\pm}78.65ng/ml$ of TGF-${\beta}$ 2 while in human, $284{\pm}124.75ng/ml$ of TGF-${\beta}$ 1 and $29.75{\pm}6.73ng/ml$ of TGF-${\beta}$ 2. Thus, TGF-${\beta}$ is the predominant TGF-${\beta}$ isotype in bovine colostrum and vice versa in human colostrum. Both TGF-${\beta}$ isotypes diminished significantly in human and bovine colostrum with time. Next, biological activity of colostrial samples was examined in vitro. Both human and bovine colostrum increased IgA synthesis by LPS-activated mouse spleen B cells, which is a typical effect of TGF-${\beta}$ on the mouse B cell differentiation. Futhermore, we found that anti-proliferative activity in MV1LU cells by colostrum samples disappeared by addition of anti-TGF-${\beta}$ 1 and anti-TGF-${\beta}$ 2 antibody. In conclusion, there are substantial amounts of biologically active TGF-${\beta}$ 1 and TGF-${\beta}$ 2 in bovine and human colostrum. The results that the colostrum can increase IgA expression has important implications since IgA is the major Ig class produced in the gastrointestinal tract. We have previously shown that the stimulatory effect of Bifidobacteria bifidum on spllen B cells was quite similar to that of LPS which is a well-known polyclonal activator for murine B cells. In the present study, we further asked whether B. bifidum regulate the synthesis of IgA by mucosal lymphoid cells present in Peyers patches (PP) and mesenteric lymph nodes (MLN). B. bifidum alone, but not C. perfringens, significantly induced overall IgA and IgM synthesis by both MLN and PP cells. This observation indicates that B. bifidum possesses a modulatory effect on the mucosal antibody production in vivo. We, therefore, investigated the mucosal antibody prodduction following peroral administration of B. bifidum to mice. Ingested B. bifidum significantly increased the numbers of Ig (IgM, IgG, and IgA) secreting cells in the culture of both MLN and spleen cells, indicating that peroally introduced B. bifidum enhances mucosal and systemic antibody response. Importantly, however, B. bifidum itself does not induce the own specific antibody responses, implying that B. bifidum do not incite any unwanted immune reaction. Subsequently, it was found that excapsulation of B. bifidum further augments the total IgA production by increasing the number of IgA-secreting cells in the culture of both MLN and spleen cells. Finally, we found that the immuno-stimulating activity of B. bifidum is due to its cell wall components but not due to any actively secreting component(s) from bacteria. Thus our data reveal that peroral administration of B. bifidum can enhance intestinal IgA production and that encapsulation of B. bifidum further reinforces the IgA production.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.9
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• pp.1367-1373
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• 2007

The aim of this study was to determine the feeding value to sheep of Acacia saligna grown under temperate conditions. Pen trials were undertaken to determine the effects of feeding A. saligna, which had been grown in a Mediterranean environment, on feed intake, nitrogen balance and rumen metabolism in sheep. Sheep were given ad libitum access to A. saligna with or without supplementation with PEG 4,000 or PEG 6,000. PEG 4000 appears to be the major detannification agent used in trials involving high tannin feed despite the fact that PEG 6000 has been shown to be more effective, in vitro. For this reason it was of interest to compare the two, in vivo. Dry matter intake was greater (p<0.05) in sheep supplemented with either PEG 4,000 or PEG 6,000 compared to the control. There was no difference, however, in intake between those supplemented with either PEG 4,000 or 6,000. Although animals were not weighed throughout the trial, a loss in body condition was obvious, in particular in the control group. Intake of N was greater (p<0.05) in sheep supplemented with either PEG 4,000 or PEG 6,000 than in the control. There was no difference in N intake between those supplemented with either PEG 4,000 or PEG 6,000. There were no significant differences in either the faecal or urinary N output between any of the treatment groups and all treatment groups were in negative N balance. Neither the average nor maximum pH of ruminal fluid of the control group was different to those supplemented with PEG. The minimum pH for the control group, however, was significantly higher (p<0.05) than for either of the PEG treatments. The average and the maximum ammonia levels were lower (p<0.05) in the control group compared with those in either of the PEG treatment groups. For all dietary treatments ruminal ammonia levels were well below the threshold for maximal microbial growth. Feeding A. saligna, without PEG, had a definite defaunating effect on the rumen. For all dietary treatments ruminal ammonia levels were well below the threshold for maximal microbial growth. It was concluded that A. saligna was inadequate as the sole source of nutrients for sheep, even with the addition of PEG 4,000 or PEG 6,000. The anti-nutritional effects on the animals were largely attributed to the excessive biological activity of the phenolics in the A. saligna leaves. There is a need to determine other supplements that may be complimentary with PEG to enhance the nutritive value of A. saligna to maintain a minimum of animal maintenance.