• Journal of Yeungnam Medical Science
• /
• v.17 no.1
• /
• pp.1-11
• /
• 2000

Inhibition of cyclooxygenase(COX), and thus prevention of the formation of prostaglandins, provided a unifying explanation of the therapeutic and toxic actions of nonsteroidal anti-inflammatory drugs (NSAIDs). Recently, the discovery of the two isoforms of COX was made by molecular biologists studying neoplastic transformation in chick embryo cells. The constitutive enzyme, COX-1, is obviously responsible for the production of prostaglandins involved in housekeeping functions such as maintenance of integrity of the gastric mucosa, renal blood flow and platelet aggregation. The inducible form of COX (COX-2) is responsible for the formation of prostaglandins that pathologically affects inflammation, pain and fever. Clearly, all the experimental and clinical data support the hypothesis that the beneficial effects of NSAIDs are due to inhibition of the COX-2 enzyme, whereas the gastrotoxicity is due to inhibition of COX-1. The cox-2/COX-1 ratios of the NSAIDs in common use have been measured and compared with epidemiological data on their side effects. There is little evidence to suggest that one NSAID is clearly more effective than another, But substantial individual variability is present with respect to the pharmacology and pharmacokinetics of these drugs: therefore it is essential to adjust the dosage and choose specific drug to the patient's response.

• Tuberculosis and Respiratory Diseases
• /
• v.66 no.4
• /
• pp.274-279
• /
• 2009

Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-$\gamma$) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-$\gamma$ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.05a
• /
• pp.13-14
• /
• 2003

Ceramide, a potential cell death marker formed by sphingomyelinase, is involved in the expression of cyclooxygenase-2 (COX-2). This study examines the effect of C2-ceramide (C2), a cell-permeable ceramide analog, on the LPS-inducible COX-2 expression and signaling pathways. C2 did not induce COX-2, but potentiated LPS-inducible COX-2 expression in Raw264.7 cells, whereas dihydro-C2 was inactive.(omitted)

• Radiation Oncology Journal
• /
• v.25 no.3
• /
• pp.145-150
• /
• 2007

Purpose: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). Materials and Methods: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: $44{\sim}65.1$ Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. Results: The median length of follow-up was 13.3 months (range:$6{\sim}83$ months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p<0.05). The median survival of patients with staining for COX-2 that was positive in less than 75% of tumor cells and in at least 75% of tumor cells was 15.5 and 13.0 months, respectively (p>0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). Conclusion: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.

• 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.

• Molecules and Cells
• /
• v.37 no.10
• /
• pp.759-765
• /
• 2014

N-myc downstream-regulated gene 2 (NDRG2), which is known to have tumor suppressor functions, is frequently down-regulated in breast cancers and potentially involved in preventing the migration and invasion of malignant tumor cells. In the present study, we examined the inhibitory effects of NDRG2 overexpression, specifically focusing on the role of cyclooxygenase-2 (COX-2) in the migration of breast cancer cells. NDRG2 overexpression in MDA-MB-231 cells inhibited the expression of the COX-2 mRNA and protein, the transcriptional activity of COX-2, and prostaglandin $E_2$ ($PGE_2$) production, which were induced by a treatment with phorbol-12-myristate-13-acetate (PMA). Nuclear transcription factor-${\kappa}B$ (NF-${\kappa}B$) signaling attenuated by NDRG2 expression resulted in a decrease in PMA-induced COX-2 expression. Interestingly, the inhibition of COX-2 strongly suppressed PMA-stimulated migration and invasion in MDA-MB-231-NDRG2 cells. Moreover, siRNA-mediated knockdown of NDRG2 in MCF7 cells increased the COX-2 mRNA and protein expression levels and the PMA-induced COX-2 expression levels. Consistent with these results, the migration and invasion of MCF7 cells treated with NDRG2 siRNA were significantly enhanced following treatment with PMA. Taken together, our data show that the inhibition of NF-${\kappa}B$ signaling by NDRG2 expression is able to suppress cell migration and invasion through the down-regulation of COX-2 expression.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.364-367
• /
• 2011

Background: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin $E_2$ ($PGE_2$) and prostaglandin $I_2$ ($PGI_2$) and that these PGs regulate biological functions of T and B cells. Methods: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to $PGE_2$ and $PGI_2$ production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. Results: Both $PGE_2$ and $PGI_2$ productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). Conclusion: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.

• Reproductive and Developmental Biology
• /
• v.28 no.2
• /
• pp.89-94
• /
• 2004

This study was conducted to determine expression of acyl-CoA synthetase 4(ACS4), which is involved in converts arachidonic acid to postaglandins, in the mouse uterus during pregnancy. In arachidonic acid metabolism, acyl-CoA synthetase plays a key role in the esterification of free arachidonic acid into membrane phospholipids. Following its release by the action of calcium dependent phospholipases, free arachidonic acid is believed to be rapidly converted to arachidonoyl-CoA and reesterified into phospholipids in order to prevent excessive synthesis of prostaglandins. Here we demonstrate that ACS4 gene are differentially regulated in the peri-implatation mouse uterus. During the preimplantation period(days 0.5∼3.5), the ACS4 gene was expressed in the uterus until day 3.5 after which the expression was downregulated. The expression of cPLA2, COX1, and COX2 gene was similar to that of ACS4 gene in the preimplantation periods. However expression levels of COX1 gene show much variation on the various days of pregnancy examined. These data, suggest that ACS4 expression in preimplantation period is involved in initial attachment reaction with cPLA2, COX1, and COX2 gene.

• YAKHAK HOEJI
• /
• v.51 no.5
• /
• pp.313-317
• /
• 2007

A series of luotonin A homologues and their aza-analogues were prepared and evaluated their inhibitory activities on COX-1 and 2 as well as their selectivities on COX-2. The aza-analogue of dimethylene-bridged homologue of luotonin A, 3,3'-dimethylene-2-(1',8'-naphthyrid-2'-yl)-4(3H)-quinazolinone (2b), exhibited strongest inhibitory activity against COX-1 and COX-2 dependent phase of prostaglandin $D_2$ generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with an $IC_{50}$ of 39.3 and $1.89{\mu}M$, respectively. Selectivity of 2b on COX-2 over COX-1 was 21 which implied 2b can be a potential lead for the development of selective COX-2 inhibitor.

• Journal of Pharmacopuncture
• /
• v.20 no.3
• /
• pp.207-212
• /
• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.