• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.2
• /
• pp.568-573
• /
• 2003

We invesgated the GBH water extracts can be used as a potential cancer chemopreventive agent in humans, especially in hepatological cancer cell lines. The GBH was found to act as an potent inhibitor of COX-I only, but not as COX-2 inhibitor. Furthermore, the extract mediated anti-inflammatory effects and inhibited COX-associated hydroperoxidase functions(antipromotion activity). Inhibitory effect of the GBH water extracts on the growth of cancer cell lines such as HepG2 cell and Hep3B cell was shown.

• IMMUNE NETWORK
• /
• v.3 no.3
• /
• pp.201-210
• /
• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.227.1-227.1
• /
• 2002

Cyclooxygenase (Cox-2) is involved in tumorigenesis. hence. considered to be a molecular target for chemoprevention and chemomodulation. Selective Cox-2 inhibitors including Celecoxib and Nimesulide have been studied for their anticancer activity when given alone and in combination with radiation or cytotoxic agents. In this study, we synthesized more than 140 analogues of Celecoxib and Nimesulide. and evaluated their inhibitory effects on Cox-l and Cox-2 activity as well as cytotoxicity in order to find promising anticancer agents having selective Cox-2 inhibitory effect. (omitted)

• Korean Journal of Clinical Pharmacy
• /
• v.11 no.1
• /
• pp.45-47
• /
• 2001

• Environmental Analysis Health and Toxicology
• /
• v.21 no.3 s.54
• /
• pp.275-282
• /
• 2006

In order to get insight into the mechanism of cadmium (Cd)-induced brain injury, we investigated the effects of Cd on the induction of COX-2 in bEnd.3 mouse brain endothelial cells. Cd induced COX-2 expression and $PGE_2$ release, which were attenuated by thiol-reducing antioxidant N-acetylcysteine (NAC) indicating oxidative components might contribute to these events. Indeed, Cd increased cellular reactive oxygen species (ROS) level and DNA binding activity of nuclear factor-kB (NF-kB), an oxidative stress sensitive transcription factor. Cd-induced $PGE_2$ production and COX-2 expression were significantly attenuated by Bay 11 7082, a specific inhibitor of NF-kB and by SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK). These data suggest that Cd induces COX-2 expression through activation of NF-kB and p38 MAPK, the oxidative stress-sensitive signaling molecules, in brain endothelial cells.

• Journal of Ginseng Research
• /
• v.43 no.2
• /
• pp.319-325
• /
• 2019

Background: Ginsenoside Rf is a ginseng saponin found only in Panax ginseng that affects lipid metabolism. It also has neuroprotective and antiinflammatory properties. We previously showed that Korean Red Ginseng (KRG) inhibited the expression of cyclooxygenase-2 (COX-2) by hypoxia via peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$). The aim of the current study was to evaluate the possibility of ginsenoside Rf as an active ingredient of KRG in the inhibition of hypoxia-induced COX-2 via $PPAR{\gamma}$. Methods: The effects of ginsenoside Rf on the upregulation of COX-2 by hypoxia and its antimigration effects were evaluated in A549 cells. Docking of ginsenoside Rf was performed with the $PPAR{\gamma}$ structure using Surflex-Dock in Sybyl-X 2.1.1. Results: $PPAR{\gamma}$ protein levels and peroxisome proliferator response element promoter activities were promoted by ginsenoside Rf. Inhibition of COX-2 expression by ginsenoside Rf was blocked by the $PPAR{\gamma}-specific$ inhibitor, T0070907. The $PPAR{\gamma}$ inhibitor also blocked the ability of ginsenoside Rf to suppress cell migration under hypoxia. The docking simulation results indicate that ginsenoside Rf binds to the active site of $PPAR{\gamma}$. Conclusions: Our results demonstrate that ginsenoside Rf inhibits hypoxia induced-COX-2 expression and cellular migration, which are dependent on $PPAR{\gamma}$ activation. These results suggest that ginsenoside Rf has an antiinflammatory effect under hypoxic conditions. Moreover, docking analysis of ginsenoside Rf into the active site of $PPAR{\gamma}$ suggests that the compound binds to $PPAR{\gamma}$ in a position similar to that of known agonists.

• Radiation Oncology Journal
• /
• v.21 no.3
• /
• pp.216-221
• /
• 2003

Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.2
• /
• pp.242-248
• /
• 2010

The present study was designed in order to determine whether Lonicerae flos (LF) could mitigate rheumatoid arthritis through inhibition of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 by regulation of macrophage migration inhibitory factor (MIF). We found that MIF mRNA expression in synoviocytes stimulated with phorbol-12-myristate-13-acetate dose-dependantly decreased by LF extract treatment (0.4 - 1.0 mg/$m{\ell}$). The distribution of MIF, COX-2 and MMP-9 positive reacted cells in LPS induced arthritis of mice were decreased by LF (45 mg/kg/day) treatment for 28 days. These data likely indicate that LF may act as MIF inhibitor and may be possible to develop useful agent for rheumatoid arthritis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9967-9972
• /
• 2014

In order to prove whether downregulation of COX-2 (Cyclooxygenase-2) could modulate the epithelial-mesenchymal transition (EMT) of breast cancer, celecoxib and siRNA were respectively used to inhibit COX-2 function and expression in MDA-MB-231 cells. The EMT reversal effect in the RNAi treated group was better than that of the celecoxib group while there were no obvious differences in the medium $PGE_2$ levels between the two groups. The results show that COX-2 pathways may contribute considerably to EMT of breast cancer cells, partially dependent on the PGE2 cascade. Akt2, ZEB2 and Snail were measured to clarify the underlying mechanisms of COX-2 on EMT; COX-2 may modulate EMT of breast cancer by regulating these factors. This finding may be helpful to elucidate the mechanisms of selective COX-2 inhibitor action in EMT modulation in breast cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1655-1659
• /
• 2016

Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an $IC_{50}$ value of $40{\mu}M$. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells.