• Proceedings of the PSK Conference
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• 2003.04a
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• pp.190.2-191
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• 2003

Production of prostaglandins involved in renal salt and water homeostasis is modulated by regulated expression of the inducible form of cyclooxygenase-2 (COX-2) at restricted sites in the rat kidney. COX-2 expression in the kidney is regulated by dietary salt intake, but the mechanism of its action is not fully understood. We have previously that high salt regulates COX-2 expression in rat kidney. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9693-9698
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• 2014

Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2) gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was to comprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials and Methods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China national knowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated on Aug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A total of 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significant associations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model (pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, we also found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationship with BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in either population-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: This present meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous low-penetrant risk factor for developing BC.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.119-125
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• 2021

Background: Korean Red Ginseng (KRG) is a natural product with antiinflammatory and anticarcinogenic effects. We have previously reported that the endocrine-disrupting compound bisphenol A (BPA)-induced cyclooxygenase-2 (COX-2) via nuclear translocation of nuclear factor-kappa B (NF-κB) and activation of mitogen-activated protein kinase and promoted the migration of A549. Here, in this study, we assessed the protective effect of KRG on the BPA-induced reactive oxygen species (ROS) and expression of COX-2 and matrix metalloproteinase-9 (MMP-9) in A549 cells. Methods: The effects of KRG on the upregulation of ROS production and COX-2 and MMP-9 expression by BPA were evaluated by fluorescence-activated cell sorting (FACs) analysis, quantitative reverse transcription polymerase chain reaction, and western blotting. Antimigration ability by KRG was evaluated by migration assay in A549 cells. Results: KRG significantly suppressed the BPA-induced COX-2, the activity of NF-κB, the production of ROS, and the migration of A549 cells. These effects led to the downregulation of the expression of MMP-9. Conclusions: Overall, our results suggest that KRG exerts an antiinflammatory effect on BPA-treated A549 cells via the suppression of ROS and downregulation of NF-κB activation and COX-2 expression which leads to a decrease in cellular migration and MMP-9 expression. These results provide a new possible therapeutic application of KRG to protect BPA-induced possible inflammatory disorders.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.154-155
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• 2001

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of proinflammatory agents and cytokines. COX-2 expression has been shown to be elevated in several different types of human cancer. The presence of oncogenic ras has been associated with constitutive induction of COX-2 in certain H-ras transformed cells, and COX-2 overexpression confers resistance to apoptosis.(omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.244.1-244.1
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• 2002

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.70.1-70.1
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• 2003

Celecoxib, the selective cyclooxygenase-2 (COX-2) inhibitor, has recently been reported to reduce the formation of polyps in patients with familial adenomatous polyposis. This specific COX-2 inhibitor also protects against experimentally induced carcinogenesis, but molecular mechanisms underlying its chemopreventive activities remain largely unresolved. In the present work, we found that celecoxib inhibited 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced expression of COX-2 in female ICR mouse skin when applied topically 30 min prior to TPA as determined by both immunoblot and immunohistochemical analyses. (omitted)

• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.348-352
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• 2007

Inflammation is a complex process resulting from a variety of mechanisms. Combined inhibition of the activities of enzymes involved in the process may therefore be considered more important in anti-inflammatory property of plant extracts than any single contribution. In this study, the inhibitory effects of the ethanol extracts of thirty plant foods on the activities of secretory phospholipase $A_{2}$ ($sPLA_{2}$), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 12-lipoxygenase (12-LOX) were examined. Several legumes, mungbean sprout and some leaf vegetables inhibited the activity of $sPLA_2$, upstream enzyme of inflammation pathway. Only soybean sprout and mungbean sprout significantly inhibited 12-LOX activity. Although most of extracts inhibited the activities of both COX-1 and COX-2, water dropwort and amaranth showed selectivity for the inhibition of COX-2 over COX-1. Especially, mungbean showed anti-inflammatory property at both upstream and downstream of inflammation pathway with relatively low $IC_{50}$ values for $sPLA_{2}$ and COX-2 enzymes. Mungbean sprout exhibited inhibitory effects on all enzymes related to early and late inflammation and soybean sprout suppressed 12-LOX and COX-2 simultaneously, although the activities of these plants were showed at relatively high concentration. Therefore, mungbean, mungbean sprout, and soybean sprout appear to exhibit anti-inflammatory effects by combined inhibition of inflammatory enzymes.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4453-4458
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• 2012

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears to be involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of Tan II-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 and VEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg of Tan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluated microvascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected into HCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2 mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibit tumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effects of Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectively inhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2 and VEGF.

• Journal of Acupuncture Research
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• v.17 no.2
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• pp.187-208
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• 2000

By the activation of ovary hormone, many morphological changes occur in the epithelial cell lines and muscle cells in rat uterus. These two cells in uterus are important to the implantation of embryo, maintaining pregnancy and starting parturition. One important change associated with the morphological change of these two cells in uterus is the change on prostaglandin(PG) metabolism. Its presence and synthesis in endometriurn and myometrium in uterus affects estrous cycle and the start of embryo implantation in uterus. It also performs as an important modulator in parturition. So the abnormally weak expression of PG causes difficulty during labor and over-expression causes pre-term labor. PG biosynthesis starts from either free or liberated arachidonic acids from membrane phospholipid by phospholipase. Such arachidonic acids are converted into PG catalyzed by Cyclooxygenase. Under normal physiological condition, Cyclooxygenase-1(COX-1) having 602 units of amino acids controls the synthesis of PG. It acts as a local hormone regulating vasomodulation of blood flow, flexible muscle movement, increasing the blood permeability and contributing the protective role in preserving integrity of the stomach lining and Cyclooxygenase-2 (COX-2) is induced by the inflammation, pregnancy and increased its expression until parturition. Lipid metabolite like PG is located in uterine and expression of COX-2 increased with pregnancy. Increased expression of COX proteins in epithelial cells and myometrial cells are told to increase the muscle contractility in uterus but decreased right after the labor in rat. It is a good sign indicating that COX proteins are deeply related to the start of labor. Currently, Several studies report the use of PG and COX-2 inhibitor as medication for controlled abortion or to prevent pre-term labor but they entail various side-effects. Our study proposed to suggest use of acupuncture as an another mediator to control abortion or pre-term labor without causing unnecessary side-effects by those medicines. Two acupuncture sites, LI-4 & SP-6 were selected due to their known efficacy. From the immunohistochemical staining of COX-2, normal expression of COX-2 protein in nonpregnant SD rat's uterus revealed that COX-2 protein was primarily detected in the lumina epithelial lining and in the epithelial cell lining contacting the stromal cells. High resolution optical microscopic scanning revealed distinguishable staining in the myometrial mucosa. LI-4 acupuncture administered nonpregnant rat's uterus showed strong expression for COX-2 in endometrium contacted with lumina epithelial lining of rat uterus and in myometrial mucosa. Stromal cells showed more staining than untreated nonpregnant rat's uterus and stronger staining in stromal cells contacting myometrial layer compared to untreated nonpregnant rat's uterus. SP-6 acupuncture administered nonpregnant rat's uterus showed weak expression for COX-2 in myometrial layers and stromal cells but no staining was visible in lumina epitheliai and glandular epithelial cells. Few stromal cells and myometrial mucosa were positively stained for COX-2. Pregnant SD rat's uterus was also immunostained for COX-2 expression after 18 days of pregnancy. Unlike to untreated nonpregnant rat's uterus, luminal epithelial cells were not positively stained for COX-2 but stronger staining for COX-2 was revealed in stromal cells. LI-4 acupunctured SD rat's uterus had very strong expression of COX-2 in luminal epithelial lining. Few stromal cells showed stronger positive COX-2 staining and myometrial layers also showed more expression than untreated pregnant rat. SP-6 acupuncture administered pregnant SD rat's uterus showed positive expression of COX-2 in epithelial cells of luminal mucosa layer but weaker than that of LI-4 acupuncture treatment's case. However, strong positive staining was revealed in stromal mucosa and myometrial layers. Virgin SD rat's uterus motility index during LI-4 acupuncture was 66.52 % (Prob〉T = 0.0197) compared to its motility before the acupuncture treatment but the motility index was slighdy elevated up to 79.58 % (Prob〉T = 0.1175) after the acupuncture. During the SP-6 acupuncture treatment for 30 minutes, uterus motility index was 90.52 % (Prob〉T = 0.1832) showing lesser decrement but consequently reached similar motility index decreasal to 79.95 % (Prob〉T = 0.0215) after the acupuncture treatment as LI-4 showed. LI-4 acupuncture tend to be a quick treatment to reducing the uterus motility in a virgin rat but eventually both two acupuncture administration created very similar reduction of uterus motility seeing the index after the both acupunctures. The uterus movement monitored during the LI-4 acupuncture administered for 30 minutes, Pregnant SD rat showed decreased motility down to 77.90 % (Prob〉 T = 0.0076) compared to uterus motility before the acupuncture and it continuously decreased down to 71.81 %(Prob〉T = 0.0214) after the removal of needle. The statistical analysis using paired t-test showed significance difference for both two motility indexs at =0.05. SP-6 acupuncture administered to pregnant SD rat also had similar pattern of decreasing uterus motility index down to 74.70 % (Prob〉T = 0.1730) during the initial 30 minutes acupuncture administration and it was continuously lowered to 71.52 % (Prob〉T = 0.0155) after the acupuncture. The paired t-test resuit for SP-6 suggest prompt response of uterus motility index to the SP-6 acupuncture treatment but consequently reached same level of inducing the motility reduction as LI-4 at =0.05 level.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.607-612
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• 2001

Endogenous carbon monoxide (CO) shares with nitric oxide (NO) a role as a putative neural messenger in the brain. Both gases are believed to modulate CNS function via an increase in cytoplasmic cGMP concentrations secondary to the activation of soluble guanylate cyclase (sGC). Recently CO and NO were proposed as a possible mediator of febrile response in hypothalamus. NO has been reported to activate both the constitutive and inducible isoform of the cyclooxygenase (COX). Thus, we investigated whether CO arising from heme catabolism by heme oxygenate (HO) is involved in the febrile response via the activation of COX in the hypothalamus. $PGE_2$ which is a final mediator of febrile response released from primary cultured hypothalamic cells was taken as a marker of COX activity. $PGE_2$ concentration was measured with EIA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent inducer of HO) evoked an increase in $PGE_2$ release from hypothalamic cells, and these effects were blocked by methylene blue (an inhibitor of sGC). And membrane permeable cGMP analogue, dibutyryl-cGMP elicited significant increases in $PGE_2$release. These results suggest that there may be a functional link between HO and COX enzymatic activities. The gaseous product of hemin through the HO pathway, CO, might play a role through the modulation of the COX activity in the hypothalamus.