Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; Hep G2 Cells ; Humans ; Nitrobenzenes ; pharmacology ; Radiation Tolerance ; drug effects ; Sulfonamides ; pharmacology

No abstract available.
Carcinoma, Hepatocellular/enzymology/*metabolism/pathology ; Cell Proliferation/drug effects ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Humans ; Liver Neoplasms/enzymology/*metabolism/pathology ; Microtubule-Associated Proteins/*antagonists & inhibitors/metabolism ; Neoplasm Proteins/*antagonists & inhibitors/metabolism ; Nitrobenzenes/pharmacology ; Sulfonamides/pharmacology

The cyclooxygenase (COX) is a key enzyme in the coversion of arachidonic acid to prostaglandins. COX-1 is constitutively expressed and is a critical housekeeping gene, whereas COX-2 is rapidly upregulated by growth factors and cytokines and thus responsible for inflammation. COX-2 is frequently overexpressed in colonic adenoma and carcinoma. Specific inhibitors of COX-2 have been shown to induce apoptosis in tumor cells and to inhibit tumor growth in animal models and in humans. Long-standing IBD patients have increased risk of developing colorectal cancer compared to general population. IBD-associated colorectal carcinogenesis is probably promoted by chronic inflammation and closely related to COX-2. In a recent study, powerful chemopreventive ability of selective COX-2 inhibitor was observed in colitis-related colon carcinogenesis in mouse model. But it was reported that even selective COX inhibitors aggravated the DSS-induced colonic inflammation. It is assumed that endogenous PGs are involved in the mucosal defense against DSS-induced colonic ulcerations which are produced by COX-1 at early phase and by COX-2 at late phase. Long-term use of COX-2 inhibitors for the chemoprevention of colitic cancer is needed to define their mechanism of action, that reduce side effects and have specific tumor target.
Animals ; Colitis, Ulcerative/*drug therapy ; Colonic Neoplasms/diagnosis ; Cyclooxygenase 1/metabolism ; Cyclooxygenase 2/metabolism ; Cyclooxygenase 2 Inhibitors/pharmacology/*therapeutic use ; Humans ; Mice ; Models, Animal

This study was designed to clarify the dependency of hypoxic coronary vasodilation (HCD) on the endothelium and the role of the K+ channels on HCD in the rabbit coronary artery. HCD was investigated in an isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit (KH) solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and was maintained for 15 approximately 25 min. Hypoxia elicited a vasodilation in the precontracted coronary artery with and without endothelium. There was no difference between the amplitude of the HCD induced by two consecutive hypoxic challenges and the effects of 20% O2 + 5% CO2 + 75% N2 and 95% O2 + 5% CO2 control K-H solution of subsequent responses to hypoxia. Inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HCD. Blockades of the tetraethylammonium chloride-sensitive K+ channel abolished HCD. Apamin, a blocker of the small conductance Ca(2+)-activated K+ (KCa) channel, and iberiotoxin, a blocker of the large conductance KCa channel had no effect on HCD, respectively. Glibenclamide, a blocker of the ATP-sensitive K+ (K+ATP) channel, reduced HCD. Cromakalim, an opener of the K+ATP channel, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia while glibenclamide reduced both hypoxia- and cromakalim-induced vasodilatations. In conclusion, these results suggest that HCD is independent on endothelium and HCD is considered to be induced by activation of K+ATP channel.
Animal ; Anoxia/physiopathology* ; Coronary Vessels/physiopathology* ; Coronary Vessels/drug effects ; Cyclooxygenase Inhibitors/pharmacology ; Enzyme Inhibitors/pharmacology ; Female ; Indomethacin/pharmacology ; Male ; Nitroarginine/pharmacology ; Rabbits ; Tetraethylammonium/pharmacology ; Vasodilation/physiology*

The inhibitory ratio (1%) of artificial musk on cyclooxygenase-2 (COX-2) was determined by enzyme immunoassay (EIA). The dose-effect relationship between concentrations of artificial musk and 1% was established. It was found that artificial musk had obvious inhibitory action on COX-2. The concentration for 50% of maximum inhibitory effect (IC50) was about 2.26 mg x mL(-1). There was a good relationship between the logarithm concentrations of artificial musk and 1% when the concentrations of artificial musk ranged from 0.31-20.0 mg x mL(-1). The results indicated that this EIA method could be applied to evaluate the anti-inflammatory activity of artificial musk quickly, conveniently, sensitively and exactly. This paper provided a novel method and foundational research for the bioassay of artificial musk.
Anti-Inflammatory Agents ; pharmacology ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Fatty Acids, Monounsaturated ; pharmacology ; Immunoenzyme Techniques ; methods ; Inhibitory Concentration 50 ; Quantitative Structure-Activity Relationship

OBJECTIVETo study the inhibitory effects of c9, t11-conjugated linoleic acid (c9, t11-CLA) on migration of human gastric carcinoma cell line (SGC-7901) via cyclooxygenase-2 (COX-2) pathway.

METHODSAfter inhibiting COX-2 activity by 100 micromol/L COX-2 inhibitor NS-398 in SGC-7901 cell, we treated SGC-7901 cells with c9, t11-CLA at a concentration of 200,100, 50, 25 micromol/L for 24 h, respectively. Using reconstituted basement membrane invasion, adhesion, chemotaxis assays, we detected the effect of c9, t11-CLA and COX-2 on the cell migration.

RESULTSCompared to NS-398 group, 200, 100 micromol/L c9, t11-CLA significantly suppressed SGC-7901 cells invading into the reconstituted basement membrane (F = 14.309, P = 0.000; F = 19.005, P = 0.000). 200 micromol/L c9, t11-CLA significantly inhibited SGC-7901 cells adhering to laminin, fibronectin and Matrigel (F = 3.063, P = 0.021; F = 6.692, P = 0.001; F = 11.999, P = 0.000). The chemotaxis of SGC-7901 cells and inhibitory frequency were significantly decreased in the 200 micromol/L c9, t11-CLA group (F = 1.380, P = 0.276).

CONCLUSIONc9, t11-CLA inhibits invasion, adhesion and chemotaxis of SGC-7901 cells, and the COX-2 plays an important role in the process. [ Key words]

Cell Movement ; drug effects ; physiology ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Humans ; Linoleic Acid ; metabolism ; pharmacology ; Neoplasm Invasiveness ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured

OBJECTIVETo investigate the effects of the selective cyclooxygenase-2 (COX-2) inhibitor NS398 on the growth of human pancreatic tumor BxPC-3 cell strain and its possible mechanisms.

METHODSThe effect of NS398 on cell growth was assessed by 3- (4,5-dimethylthiazol-2-yl) -2, 5-diphenyl thiazolyl blue (MTT) assay. Apoptosis was determined by fluorescence-activated cell scanning (FACS) analysis and assessment of the floating cell/attached cell ratio. Caspase-3 activation was evaluated by Active Caspase-3 Apoptosis Kit with flow cytometry. Reverse transcriptase-polymerase chain reaction analysis (RT-PCR) and Western blot were used to demonstrate expression levels of COX-1, COX-2 mRNA, and protein, as well as Caspase-3 protein in pancreatic tumor BxPC-3 cell strain.

RESULTSSelective COX-2 inhibitor NS398 significantly decreased cell viability and induced apoptosis in pancreatic tumor BxPC-3 cell strain. The protein expression of Caspase-3 was induced by high-concentration NS398. Caspase-3 activity was strongly activated by NS398.

CONCLUSIONSSelective COX-2 inhibitor NS398 has antiproliferative and proapoptotic potential in pancreatic tumor BxPC-3 cells. Such effect is independent of COX-2, but correlates with Caspase-3 activation.

Apoptosis ; drug effects ; Caspase 3 ; drug effects ; metabolism ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; pharmacology ; Humans ; Nitrobenzenes ; pharmacology ; Pancreatic Neoplasms ; enzymology ; pathology ; Sulfonamides ; pharmacology ; Tumor Cells, Cultured

Animals ; Brain Ischemia ; drug therapy ; Cyclooxygenase Inhibitors ; pharmacology ; Flurbiprofen ; analogs & derivatives ; Male ; Neuroprotective Agents ; pharmacology ; PPAR gamma ; physiology

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.
Phospholipases A/antagonists & inhibitors ; Phenols/*pharmacology ; Peroxisome Proliferator-Activated Receptors/drug effects/physiology ; NF-kappa B/metabolism ; Lipoxygenase Inhibitors/pharmacology ; Humans ; Flavonoids/*pharmacology ; Cytokines/biosynthesis ; Cyclooxygenase Inhibitors/pharmacology ; Arachidonic Acid/metabolism ; Anti-Inflammatory Agents/*pharmacology ; Animals

Although hypoxic pulmonary vasoconstriction (HPV) has been recognized by many researchers, the precise mechanism remains unknown. As isolated pulmonary arteries will constrict in vitro in the response to hypoxia, the oxygen sensor/transduction mechanism must reside in the pulmonary arterial smooth muscle or in the endothelium, or in both. Unfortunately, much of the current evidence is conflicting, especially as to the dependency of HPV on the endothelium and the role of a K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPV on the endothelium and the role of a K+ channel on HPV in rat pulmonary artery. The effects of hypoxia were investigated in isolated main pulmonary arteries precontracted with norepinephrine. Vascular rings were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 + 5% CO2 and this was maintained for 20 min. Hypoxia elicited a vasoconstriction in arteries with endothelium. Mechanical disruption of the endothelium abolished HPV. There was no difference between the amplitude of the HPV induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on a subsequent response to hypoxia. Inhibition of NO synthesis by treatment with N(omega)-nitro-L-arginine reduced HPV, but inhibition of a cyclooxygenase pathway by treatment with indomethacin had no effect on HPV. Blockades of a tetraetylammonium chloride-sensitive K+ channel abolished HPV. Verapamil, a Ca2+ entry blocker reduced HPV. In conclusion, these results suggest that HPV was dependent on the endothelium and that HPV can be considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation such as the opening of a K+ channels.
Animal ; Anoxia/physiopathology* ; Blood Vessels/physiopathology ; Calcium Channel Blockers/pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Enzyme Inhibitors/pharmacology ; Indomethacin/pharmacology ; Nitroarginine/pharmacology ; Pulmonary Circulation/physiology* ; Pulmonary Circulation/drug effects ; Rats ; Tetraethylammonium/pharmacology ; Vasoconstriction/physiology* ; Vasoconstriction/drug effects ; Verapamil/pharmacology