• Natural Product Sciences
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• v.18 no.4
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• pp.211-214
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• 2012

Since 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key metabolic enzyme of prostaglandin $E_2$ ($PGE_2$), inhibition of 15-PGDH is supposed to facilitate various physiological functions by increasing $PGE_2$. Methanol extract of Artemisia argyi (AAME) inhibited 15-PGDH ($IC_{50}$: $13.13{\mu}g/mL$) with relatively low cytotoxicity ($IC_{50}$: $415.00{\mu}g/mL$) and elevated extracellular $PGE_2$ levels in HaCaT cells. Real-time PCR analysis showed that AAME decreased significantly mRNA expression of PG transporter (PGT) in HaCaT cells. These results indicate that AAME could be applicable to functional materials as a 15-PGDH inhibitor and PGT expression inhibitor for the upregulation of extracellular $PGE_2$ level.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.33-40
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• 2013

Objectives : To study the apoptosis effects of fermented Undaria pinnatifida extracts(FUP) against HCT-15 colon cancer cells. Method : By measuring cell proliferation, DNA fragmentation, cell cycle, morphology, and western blot from FUP, the study investigated the effects of the extractions had upon the HCT-15 colon cancer cells, and concluded that the inhibiting effects upon cells were induced by apoptosis. Result : FUP effectively inhibited the growth of HCT-15 colon cancer cells. After analyzing the DNA fragmentation, the study observed a DNA ladder, while examining the cells, and found an increase of sub-G1 hypodiploid cells. On the changes regarding the nucleus of the cells, a condensation of cells and chromatin, as well as an apoptotic body was clearly observed. By observing through western blot from FUP, the study found a decreased level of Bcl-2 from HCT-15 colon cancer cells, but the increased level of Bax and cleaved caspase-3, which as a result induced apoptosis, inhibiting the growth of HCT-15 colon cancer cells. FUP increased the natural death of HCT-15 colon cancer cells by the induction of apoptosis. FUP seemed to have no suppressing effect upon HL-60/MX2 cells. However, compared to the fucoidan, the study was able to clearly observe morphological changes of HCT-15 cells apoptosis, in a 1/2 concentration. Conclusion : FUP had antiproliferative effects on different kinds of cancer cells, while proving especially efficacious against colon cancer cells.

• BMB Reports
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• v.41 no.3
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• pp.230-235
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• 2008

LRP15 is a novel gene cloned from lymphocytic cells, and its function is still unknown. Bioinformatic data showed that LRP15 might be regulated by DNA methylation and had an important role in DNA repair. In this study, we investigate whether the expression of LRP15 is regulated by DNA methylation, and whether overexpression of LRP15 increases efficiency of DNA repair of UV-induced DNA damage in HeLa cells. The results showed (1) the promoter of LRP15 was hypermethylated in HeLa cells, resulting a silence of its expression. Gene expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine, but not by a histone deacetylase inhibitor, trichostatin A; (2) overexpression of LRP15 inhibited HeLa cell proliferation, and the numbers of cells in the G2/M phase of the cell cycle in cells transfected with LRP15 increased about 10% compared with controls; (3) cyclin B1 level was much lower in cells overexpressing LRP15 than in control cells; and (4) after exposure to UV radiation, the LRP15-positive cells showed shorter comet tails compared with the LRP15-negative cells. From these results we conclude that the expression of LRP15 is controlled by methylation in its promoter in HeLa cells, and LRP15 confers resistance to UV damage and accelerates the DNA repair rate.

• BMB Reports
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• v.52 no.8
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Korean Journal of Veterinary Research
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• v.27 no.2
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• pp.191-200
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• 1987

Attempts were to produce porcine leukocyte interferon(PorLeIF) and porcine immune interferon (PorIIF) in the culture of porcine leukocytes. The interferons produced were tested for antiviral activity against vesicular stomatitis virus on poreine-derived PK(15) cells, human-derived FL cells, and Korean native black goat-derived BGK cells. The results were summarized as follws: 1. In the isolation of porcine leukocytes, the mean isolation rate by the buffy coat separation method (28.7%) was higher than that by the hydroxyethyl starch-RBC sedimentation method (9.2%). 2. When NDV(BI)-induced PorLeIFs were assyed on PK(15) cells and FL cells, the mean titers were 129 IU/ml and 72 IU/ml respectively, being 55.8% of the activity in homologous species system expressed in heterologous system. 3. The activities of PHA P-induced PorIIFs were 197 IU/ml on PK (15) cells and no activity on human FL cells. The mean antiviral activity of PorIIF was 1.5 times that of PorLeIF in PK (15) cells. 4. The cytopathic effect of vesicular stomatitis virus was observed in BGK cells derived from Korean native black goat kidney permitting interferon assay on the cells. While the cross-species antiviral activity of reference human ${\alpha},\;{\beta}-interferon$ was observed on the cells, PorLeIF and PorIIF did not show any activity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.14-40
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• 2002

15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.383-388
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• 2011

Regulators of G-protein signaling (RGS) proteins are regulators of $Ca^{2+}$ signaling that accelerate the GTPase activity of the G-protein ${\alpha}$ -subunit. RGS1, RGS2, RGS4, and RGS16 are expressed in the pancreas, and RGS2 regulates G-protein coupled receptor (GPCR)-induced $Ca^{2+}$ oscillations. However, the role of RGS4 in $Ca^{2+}$ signaling in pancreatic acinar cells is unknown. In this study, we investigated the mechanism of GPCR-induced $Ca^{2+}$ signaling in pancreatic acinar cells derived from $RGS4^{-/-}$ mice. $RGS4^{-/-}$ acinar cells showed an enhanced stimulus intensity response to a muscarinic receptor agonist in pancreatic acinar cells. Moreover, deletion of RGS4 increased the frequency of $Ca^{2+}$ oscillations. $RGS4^{-/-}$ cells also showed increased expression of sarco/endoplasmic reticulum $Ca^{2+}$ ATPase type 2. However, there were no significant alterations, such as $Ca^{2+}$ signaling in treated high dose of agonist and its related amylase secretion activity, in acinar cells from $RGS4^{-/-}$ mice. These results indicate that RGS4 protein regulates $Ca^{2+}$ signaling in mouse pancreatic acinar cells.

• The Journal of Natural Sciences
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• v.16 no.1
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• pp.143-154
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• 2005

To define the ecological roles of bacterial community in Daechung Reservoir. Vertical variation of total bacterial numbers were estimated at MAN site for one year with DAPI staining. The bacterial numbers were counted, environmental factors were monitored at the surface, -5m, -10m, -15m and -25 m of MAN sited and tried to explain the vertical bacterial numbers with environmental factors. The bacterial number was $1.6-1.7.0 x10^6$ cells/ml at the surface, $2.3-11.0x10^6$ cells/ml at 5 m depth, $1.2-1.4.0x10^6$ cells/ml at 10 m depth, $1.4-15.0x10^6$ cells/ml at 15 m depth and $1.4-1.3.0x10^6$ cells/ml at 25 m depth. The Mean bacterial number at the surface was more that those at any other depth. The explanation of the vertical total bacterial numbers with environmental factors were suggested.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• Molecules and Cells
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• v.24 no.3
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• pp.323-328
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• 2007

SOX (Sry-related HMG box) family proteins, which have an evolutionarily conserved DNA binding domain, have crucial roles in cell differentiation. However, their target genes remain enigmatic. Some members of the SOX family may have roles in regulation of cell proliferation. We established stable NT2/D1 cell lines overexpressing SOX15 (SOX15-NT2/D1), and a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the SOX15-NT2/D1 cells exhibited significantly slower growth than the controls. Flow cytometry analysis revealed that an increased fraction of the SOX15-NT2/D1 cells were in G1-G0. In addition, a microarray analysis identified 26 genes that were up-regulated in the SOX15-NT2/D1 cells, but none that were down-regulated genes. Among the up-regulated genes, IGFBP5, S100A4, ID2, FABP5, MTSS1, PDCD4 have been shown to be related to cell proliferation and/or the cell cycle.