• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.623-629
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• 2016

(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1), a marine cembrenolide diterpene, has anticancer activity against colon cancer cells such as HT-29, SNU-C5/5-FU (fluorouracil-resistant SNU-C5) and SNU-C5. However, the action mechanism of LS-1 on SNU-C5 human colon cancer cells has not been fully elucidated. In this study, we investigated whether the anticancer effect of LS-1could result from apoptosis via the modulation of $Wnt/{\beta}$-catenin and the TGF-${\beta}$ pathways. When treated with the LS-1, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3 and cleavage of poly (ADP-ribose) polymerase in SNU-C5 cells. Furthermore, the apoptosis induction of SNU-C5 cells upon LS-1 treatment was also accompanied by the down-regulation of $Wnt/{\beta}$-catenin signaling pathway via the decrease of GSK-$3{\beta}$ phosphorylation followed by the decrease of ${\beta}$-catenin level. In addition, the LS-1 induced the activation of TGF-${\beta}$ signaling pathway with the decrease of carcinoembryonic antigen which leads to decrease of c-Myc, an oncoprotein. These data suggest that the LS-1 could induce the apoptosis via the down-regulation of $Wnt/{\beta}$-catenin pathway and the activation of TGF-${\beta}$ pathway in SNU-C5 human colon cancer cells. The results support that the LS-1 might have potential for the treatment of human colon cancer.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.1
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• pp.65-72
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• 2009

Skin aging appears to be principally attributed to a decrease in both levels of Type I collagen and regeneration ability of dermal fibroblasts. It is important to introduce an efficient and safe agent for effective management of skin aging. To this end, we performed screening for anti-ageing agents and then found that vegetable peptones (pea and wheat) promoted cell proliferation of adult stem cells. Vegetable peptones may be considered as useful medium additives because it can supply nutrients, peptides, amino acids or growth factor analogues. This study was designed to investigate effects of vegetable peptones on cell proliferation/collagen production and their possible mechanisms in human dermal fibroblasts. In cell proliferation assay, vegetable peptones significantly promoted cell proliferation in a concentration-dependent manner. In addition, human COL1A2 promoter luciferase and type I procollagen synthesis assays showed that vegetable peptones induce type I procollagen production through the activation of COLlA2 promoter. In both TGF-${\beta}1$ luciferase reporter and ELISA assays, vegetable peptones was found to induce TGF-${\beta}1$ production, suggesting that vegetable peptones induce type I procollagen production through the activation of TGF-${\beta}1$. When applied topically in a human skin twice a day for an 4-week period of time, vegetable peptones did not induce any adverse reactions. Theretore, based on these results, we suggest the possibility that vegetable peptones may be considered as an attractive, wrinkle-reducing candidate for topical application.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.948-955
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• 2005

Glomerular mesangial cells (GMCs) in diverse renal diseases undergo cell proliferation and/or hypertrophy, and gangliosides have been reported to play an important role in modulating cell structure and function. This study compared the effects of transforming growth $factor-\beta\; (TGF­\beta1)$ and the effects of the application of exogenous gangliosides on GMCs and investigated whether the application of exogenous gangliosides regulated cellular proliferation and hypertrophy. Human GMCs were cultured with exogenous gangliosides and $TGF-\beta1$ in a media containing $10\%$ fetal bovine serum and in a media without the fetal bovine serum. Exogenous gangliosides biphasically changed the proliferation of human GMCs (0.1-1.0 mg/mL). A low concentration (0.1 mg/mL) of gangliosides mainly increased the number of human GMCs, whereas cellular proliferation was significantly reduced by raising the concentration of exogenous gangliosides. $TGF-\beta1$ greatly reduced the number of human GMCs in a concentration­dependent manner (1-10 ng/mL). Serum deprivation accelerated the gangliosides- and $TGF­\beta1-induced$ inhibition of mesangial cell proliferation to a greater extent. Gangliosides (1.0 mg/ mL) and $TGF-\beta1$ (10 ng/mL) both caused a significant increase in the incorporation of $[^3H]leucine$ per cell in the serum-deprived condition, whereas it was completely reversed in serum­supplemented condition. Similar results to the $[^3H]leucine$ incorporation were also observed in the changes in cell size measured by flow cytometric analysis. These results show that exogenous gangliosides modulate cell proliferation and hypertrophy in cultured human GMCs, and these cellular responses were regulated differently based on whether the media contained serum or not. Results from the present study raise new possibilities about the potential involvement of gangliosides in the development of mesangial cell proliferation and hypertrophy.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.10-18
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• 2006

Epithelial to mesenchymal transition (EMT) is an important etiologic factor for the development of peritoneal fibrosis in CAPD patients. Mesothelial cells are main source of trans-differentiated fibroblasts under stress from the bioincompatible peritoneal dialysate. In our study there was no difference in dialysate TGF-${\beta}$ and VEGF between the low and high GDP groups during an initial 12 months. However, after adjusting with D-CA125, the low GDPs group showed a significantly lower D-TGF-${\beta}$/D-CA125 and D-VEGF/CA125 during the initial 12 months. Among the adjusted peritoneal growth factors for CA125, VEGF/CA125 and TGF-b/CA125 were factors significantly associated with greater EMT in this study. Adjustment of the peritoneal growth factor for effluent CA125 (surrogate for mass of HPMCs) revealed significant association with EMT suggesting that the fibroblastoid transition from HPMCs could be affected by the amount of intraperitoneal growth factors (TGF-b, VEGF) per unit mass of HPMCs. There was significant improvement in both cell score and D-CA125 at the sixth and 12th months after switching from a high GDPs solution to a low GDPs solution. Use of icodextrin solution in patients who had average peritoneal transport showed not only better systemic effects such as decreased glucose absorption via dialysate but also preservation of the peritoneum, including less EMT and high mesothelial bulk mass. In conclusion, Therapy with low GDP solution including icodextrin may positively impact preservation of the peritoneal membrane integrity and prevention of peritoneal fibrosis with time on PD.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.216.1-216.1
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• 2001

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.217-231
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• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. We performed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.429-447
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• 1996

Transforming growth factor $-{\beta}$ is one of the polypeptide growth factors that mediate the activity of mesenchymal cells and regulate wound healing process via cell proliferation, migration and extracellular matrix formation. The purposes of this study is to evaluate the effects of transforming growth factor $-{\beta}$ on the protein synthetic activity of human periodontal ligament cells and human gingival fibroblasts. The cells which were prepared were primary cultured gingival fibroblasts and periodontal ligament cells from humans, and the fourth or sixth subpassage were used in the experiments. Cells were seeded and at a confluent state, 0, 0.5, I, 2.5, 5, 10 ng/ml $TGF-{\beta}$ and $2{\mu]Ci/ml\;[^3H]$ proline were added to the cells and cultured for 24 hours. Then, 1 and 5 ng/ml concentrations were selected and added to confluent cells and cultured for 24 and 48 hours. They were labeled with $2{\mu}Ci/ml\;[^3H]$ proline for 24 hours and a collagen assay was done by the Peterkofsky and Diegelman method. The results were presented as the mean disintegration per minute (dpm) per well and S.D. of four determinations, The results were as follows. : The total protein, collagen and noncollagenous protein synthesis in periodontal ligament cells and gingival fibroblasts were increased dose- dependently by transforming growth factor-p to 2.5-5 ng/ml concentration and decreased at 10 ng/ml concentration. The percent of collagen was slightly changed according to the concentration of transforming growth factor-po The effect of transforming growth $factor-{\beta}$ was not specific for collagen synthesis since it increased the total, noncollagenous and collagenous protein, simultaneously. In the comparison of protein synthetic activity between the human periodontal ligament cells and human gingival fibroblasts, the human gingival fibroblasts had higher activities than the human periodontal ligament cells at all times and concentrations of $TGF-{\beta}$. In the comparison of protein synthetic activity between the 24 hour effect and the 48 hour effect of $TGF-{\beta}$, the 48 hour cultured cells' synthetic activity decreased more than the 24 hour cultured cells at human periodontal ligament cells and human gingival fibroblasts. In conclusion, $TGF-{\beta}$ has important roles in the stimulation of protein synthesis in human periodontal ligament cells and human gingival fibroblasts. Thus, it may be useful for clinical application in periodontal regenerative procedures.

• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.185-196
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• 2007

Objective : This experimental Study was designed to investigate the effects of FOENICULI FRUCTUS(FF) on the change of inhibition lactate dehydrogenase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Method : FOENICULI FRUCTUS(FF)freeze dry powder and FF on the LDH activity in neuronal cells. Changes of FF on the physiological parameters(PaO2, PaCO2, MABP and HR) in crerbral ischemic rats. Effects of FF on the IL-1beta production, $TNF-{\alpha}$ production, $TGF-{\beta}$ production, and IL-10 in serum of cerebral ischemic rats. MCAO :. cytokines production of serum by drawing from femoral arterial blood after MCAO 1 hr. Reperfusion : cytokines production of serum by drawing from femoral arterial blood after reperfusion 1 hr. Results and Conclusion : 1. FF did not inhibit lactate dehydrogenase(LDH) activity in neuronal cells. 2. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) 1 hr and reperfusion 1 hr, sample group was significantly decreased $IL-l{\beta}$ production compared with control group 3. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly decreased $TNF-{\alpha}$ production compared with control group. 4. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly increased $TGF-{\beta}$ production compared with control group. 5. In serum by drawing from femoral arterial blood after reperfusion 1 hr, sample group was significantly increased IL-10 production compared with control group. This results were suggested that FF had inhibitive effect on the brain damage by inhibited LDH activity, $IL-l{\beta}$ and $TNF-{\alpha}$production, but accelerated $TGF-{\beta}$ production and IL-10 production.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.249-259
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• 2003

Objective : We aimed to identify the inhibitory effects of SocheongRyoungTang on Cytokine Production and Secretion of IgE in Highly Purified Mouse B cells. This experiment was designed to investigate the effect of SoCheongRyongTang(SCRT) on Antiallergy. Materials and Methods : We measured the cytotoxic activity for cytokines transcript expression, production of $IL-1{\beta},\;IL-4,\;IL-6,\;IL-10,\;IFN-{\gamma},\;TNF-{\alpha},\;TGF-{\beta}$ proliferation of B cell in anti-CD40mAb plus rIL-4 plus HRF stimulated murine splenic B cells and histamine in anti-CD40mAb plus rIL-4 plus HRF stimulated mast cells. Results : 1. SCRT increased the gene synthesis of $IFN-{\gamma}(m-RNA)$, the appearance of IL-10, $IFN-{\gamma}$. 2. SCRT decreased the gene synthesis of $IL-l{\beta},\;IL-4,\;TGF-{\beta}(m-RNA)$ and the appearance of $IL-l{\beta},\;IL-4,\;TGF-{\beta},\;IgE$ significantly. Conclusion : SCRT decreased the proliferation of B cell significantly. According to the above results, it is suggested that SCRT extract might be usefully applied for prevention and treatment of Allergic disease.