• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.229-239
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• 2009

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3 ${\sim}$ 3 ${\mu}g/ml$) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}M$) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}M$). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 ${\mu}g/ml$), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}M$) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 ${\mu}g/ml$) plus L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}M$), the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 ${\mu}g/ml$) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.

• Korean Journal of Cognitive Science
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• v.12 no.4
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• pp.49-56
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• 2001

When multiple features are presented in the image the computational models for stereopsis select the most activated matches through the excitatory and inhibitory interactions among all possible matches. Using the random-dot stereogram with two surfaces. we investigate whether human binocular mechanism selects the most activated matches. The dots consisting a surface lying in a fixation plane were selected randomly while each of the dots consisting the other surface was paired with each of the original dots in the following manner. After finding the position of each dots in the original random pattern we placed an additional dot to the left and to the right of the original position in each of the left and right image of a stereogram respectively. The luminance of additional dots was varied while that of the original random dots was fixed so that the hypothetical matches presumably could be activated differently. Across the luminance condition the depth of each surface was measured to examine whether matches to be selected were changed depending on the activation level of possible matches. When the luminance of two patterns was within 30% of one another observers perceived an opaque surface. Beyond this value two transparent surfaces were seen with the magnitude of perceived depth varying with relative luminance of two patterns. When original pattern was brighter one additional surface was perceived at the depth corresponding to the disparity of original pattern. When original dot was dimmer. however the depth of an additional surface corresponded to the disparity of newly introduced pattern. These results suggest that there are dynamic interactions within the matching process whereby highly activated matches inhibit weaker one.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2251-2256
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• 2015

To study effects of cellular FLICE (FADD-like IL-$1{\beta}$-converting enzyme)-inhibitory protein (c-FLIP) inhibition by RNA interference (RNAi) on sensitivity of U2OS cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, plasmid pSUPER-c-FLIP-siRNA was constructed and then transfected into U2OS cells. A stable transfection cell clone U2OS/pSUPER-c-FLIP-siRNA was screened from the c-FLIP-siRNA transfected cells. RT-PCR and Western blotting were applied to measure the expression of c-FLIP at the levels of mRNA and protein. The results indicated that the expression of c-FLIP was significantly suppressed by the c-FLIP-siRNA in the cloned U2OS/pSUPER-c-FLIP-siRNA as compared with the control cells of U2OS/pSUPER. The cloned cell line of U2OS/pSUPER-c-FLIP-siRNA was further examined for TRAILinduced cell death and apoptosis in the presence of a pan-antagonist of inhibitor of apoptosis proteins (IAPs) AT406, with or without 4 hrs pretreatment with rocaglamide, an inhibitor of c-FLIP biosynthesis, for 24 hrs. Cell death effects and apoptosis were measured by the methods of MTT assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry, respectively. The results indicated that TRAIL-induced cell death in U2OS/pSUPER-c-FLIP-siRNA was increased compared with control cells U2OS/pSUPER in the presence or absence of AT406. Flow cytometry indicated that TRAIL-induced cell death effects proceeded through cell apoptosis pathway. However, in the presence of rocaglamide, cell death or apoptotic effects of TRAIL were similar and profound in both cell lines, suggesting that the mechanism of action for both c-FLIP-siRNA and rocaglamide was identical. We conclude that the inhibition of c-FLIP by either c-FLIP-siRNA or rocaglamide can enhance the sensitivity of U2OS to TRAIL-induced apopotosis, suggesting that inhibition of c-FLIP is a good target for anti-cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7179-7186
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• 2013

Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.6
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• pp.333-339
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• 2005

B/K protein is a novel protein containing double C2-like domains. We examined the specific signaling pathway that regulates the transcription of B/K in PC12 cells. When the cells were treated with forskolin ($50{\mu}M$), B/K mRNA and protein levels were time-dependently decreased, reaching the lowest level at 3 or 4 hr, and thereafter returning to the control level. Chemicals such as dibutyryl-cAMP, cellpermeable cyclic AMP (cAMP) analogue and CGS21680, adenosine receptor $A_{2A}$ agonist, also repressed the B/K transcription. However, 1,9-dideoxyforskolin did not show inhibitory effect on B/K transcription, suggesting direct involvement of cAMP in the forskolin-induced inhibition of B/K transcription. Effect of forskolin, dibutyryl cAMP and CGS21680 was significantly reduced in PKA-deficient PC12 cell line (PC12-123.7). One cAMP-response element (CRE)-like sequence (B/K CLS) was found in the promoter region of B/K DNA, and electrophoretic mobility shift assay indicated its binding to CREM and CREB. Forskolin significantly suppressed the promoter activity in CHO-K1 cells transfected with the constructs containing B/K CLS, but not with the construct in which B/K CLS was mutated (AC：TG). Taken together, we suggest that the transcription of B/K gene in PC12 cells may be regulated by PKA-dependent mechanism.

• Korean Journal of Veterinary Service
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• v.32 no.4
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• pp.353-359
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• 2009

Interest in marine organisms as potential sources of bioactive agents has increased in recent years. The red seaweed, Callophyllis (C.) japonica, is abundant in the coastal regions of Jeju Island in South Korea. A previous study shows that C. japonica extracts have antioxidant activity and radioprotective effects. In this study, an methanol extract of C. japonica was tested whether it has antibacterial effects against the bacteria from swine. In vitro antibacterial activities of the crude extracts prepared from the C. japonica using 80 % methanol were tested for inhibitory activity against the Escherichia (E.) coli (S175), Enterococcus (E.) faecium (ATCC 51558), Salmonella (S.) Typhimurium and Staphylo-coccus (S.) aureus (ATCC 25923) by using broth dilution method. All organisms were incubated in brain heart infusion medium containing 1% extract at 0, 4, 8, 12 and 24 hrs. The 3 days-old piglets were fed an experimental diet supplemented with 1% C. japonica for 1 week. And the change of the coliform bacteria in feces were examined after supplement of C. japonica for 1 week. When the inocula containing $10^2{\sim}10^3$CFU/ml of each organism were used the extracts of C. japonica showed various degrees of antibacterial effects on all bacteria tested. The CFU value ($6.3\times10^8$CFU/ml) of C. japonica for E. coli was decreased 30% compared with vehicle controls ($9.0\times10^8$CFU/ml) after 8 hrs incubation. The proliferation rate of E. faecium was inhibited about 68% at 4 hrs, 81% at 8 hrs and 76% at 12 hrs after incubation, respectively. The proliferation rate of S. Typhimurium was inhibited about 96% at 4 hrs, 90% at 8 hrs and 72% at 12 hrs after incubation with extracts of C. japonica. The proliferation rate of S. aureus was inhibited more than 90% each time courses. Conclusively, a red seaweed extract of C. japonica was found to be effective against a number of gram negative and gram positive bacteria such as E. coli, E. faecium, S. Typhimurium, and S. aureus. The number of coliform bacteria was increased in the 1% C. japonica-treated group, as compared to those of controls. This result suggests that C. japonica extracts be added as an effective natural antibacterial agent. The precise mechanism of antibacterial effects and its application on swine industry remains to be further studied.

• Korean Journal of Weed Science
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• v.18 no.4
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• pp.333-340
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• 1998

The combined effects of primisulfuron and imazethapyr treated with piperonyl butoxide(PBO) on growth inhibition and acetolactate synthase(ALS) activity in corn were studied to identify the tolerance mechanism among corn cultivars. Pioneer 3751 IR showed resistance to primisulfuron and imazethapyr, but Pioneer 3751 and Chalok 2 were susceptible to them. Pioneer 3751 IR was tolerant to primisulfuron regardless of PBO treatment, but Pioneer 3751, Suwon 118 and Chalok 2 were more greatly inhibited by combined treatment of primisulfuron with PBO. Synergistic effect on growth inhibition in Pioneer 3751 IR, Pioneer 3751, Suwon 118 and Chalok 2 was not occurred when imazethapyr was treated with PBO, but Pioneer 3751, Suwon 118 and Chalok 2 tended to inhibit by combined treatment of imazethapyr with PBO. Pioneer 3751 IR showed higher ALS activity than Pioneer 3751 when primisulfuron or imazethapyr was treated. ALS activity was inhibited by primisulfuron at $0.01{\mu}M$ or above and imazethapyr at $1{\mu}M$ or above, and inhibitory effect on ALS activity was observed by primisufuron and imazethapyr treatments with PBO.

• Korean Journal of Weed Science
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• v.14 no.4
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• pp.280-290
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• 1994

The germination and the nutrient culture tests in the growth chamber and pot experiment under two types of soil conditions were conducted to determine the selectivity of oxyfluorfen and chlormethoxynil in crops and weeds and for characterization of selective mode of action, the absorption study was also conducted with different absorption methods and application time using $^{14}C$-oxyfluorfen. Oxyfluorfen showed more growth inhibitory effects than chlormethoxynil. In the nutrient culture test, rice growth was greatly inhibited at 2-leaf stage than at 4-leaf stage, and the shoot parts were more inhibited than the root parts. By preemergence application of both herbicides, higher growth inhibition was observed in sandy loam soil than in clay loam soil. Absorption and translocation of $^{14}C$-oxyfluorfen were higher by foliar application than by root treatment, and selectivity of crops and weed species may be explained partly by the amount of absorption.

• Korean Journal of Plant Resources
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• v.33 no.5
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• pp.428-435
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• 2020

In this study, we evaluated the inhibitory effect against cell growth and potential molecular mechanism of 100% ethanol extracts of branch from Sageretia thea in human colorectal cancer cells, HCT116. Ethanol dose-dependently extracts of STB significantly suppressed the growth of HCT116 cells through apoptosis. STB activated NF-κB signaling pathway through IκB-α proteasomal degradation and inducing p65 accumulation in nucleus. The inhibition of GSK3β by LiCl didn't affect STB mediated degradation IκB-α but STB mediated p65 accumulation in nucleus. In addition, STB phosphorylated GSK3β. Based on these findings, STB may be a potential candidate for the development of anti-cancer agents for human colorectal cancer.