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

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

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

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

Flavonoids are natural products that are ubiquitous in the natural world, with wide physiological activities and low toxic and side effects. In recent years, their anti-tumor effect has caused widespread concern and studies. According to the findings, flavonoids have prominent effects in preventing and treating lung cancer, breast cancer, colon cancer, prostate cancer, liver cancer, leukemia, ovarian cancer, gastric cancer and so on. Their anti-tumor mechanisms mainly include anti-oxidation, anti-free radical, induction of apoptosis of cancer cells, impact on cell cycle, immune regulation, inhibition of tumor angiogenesis, inhibition of COX-2, inhibition of telomerase activity and so on. This article focuses on the advance in domestic and foreign studies on anti-cancer activity and mechanism of flavonoids, in order to provide theoretical basis and research ideas for the further development and clinical application of flavonoids.
Animals ; Antineoplastic Agents ; pharmacology ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Humans

OBJECTIVE: To investigate the effect and mechanism of the selective COX-2 inhibitor NS-398 and carboplatin on the human cervical carcinoma cell line Hela. METHODS: The effect of NS-398, carboplatin, and both on the proliferation of Hela cells was assessed by methyl-thiazolyl tetrazolium (MTT) method, and the apoptosis assay and cell cycle distribution were analyzed by flow cytometry. RESULTS: NS-398, and carboplatin inhibited the growth of Hela cells in a dose and time-dependent manner. When combining carboplatin with NS-398, the combined inhibition rate was increased, which nearly equaled the inhibition rate of the double concentrations of carboplatin. Flow cytometry demonstrated that the cell cycle was redistributed: the G(1)-phase cell fraction was increased while the S-phase cell fraction was significantly decreased after the cells were treated with NS-398 (P<0.05), However,the result was just the opposite after being treated with carboplatin. The apoptotic rate was 1.48%+/-0.03% and 3.43%+/-0.02% for pre-treatment and post-treatment with NS-398 respectively (P>0.05) while the apoptotic rate was 9.32%+/-0.02% after the treatment with carboplatin (P<0.05). CONCLUSION NS-398 can inhibit the growth of Hela cells. The effect of NS-398 on Hela cells may not be related to the apoptosis. NS-398 and carboplatin can bring about synergistic effect in chemotherapy on Hela cells.
Apoptosis ; drug effects ; Carboplatin ; pharmacology ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Drug Synergism ; HeLa Cells ; Humans ; Nitrobenzenes ; pharmacology ; Sulfonamides ; pharmacology

The inhibitory effects of two kinds of selective cyclooxygenase-2 inhibitors on the proliferation of human carcinoma of larynx Hep-2 in vitro and their corresponding mechanisms were investigated. Hep-2 cells were cultured with two kinds of selective cyclooxygenase-2 inhibitors (Sc-58125 and Celecoxib) at various concentrations for 24 h. Morphological changes were observed under the phase microscopy and the growth suppression was detected by using MTT colorimetric assay. Apoptotic DNA fragments were observed by agarose gel electrophoresis, and the cell cycle and apoptotic rate were detected by flow cytometry (FCM) respectively. Hep-2 cells became rounded and detached from the culture dish after being treated with Celecoxib for 24 h, however, they remained morphologically unchanged with Sc-58125. Sc-58125 could increase G2 phase cells, whereas, Celecoxib rose G1 phase cells. Both of the two effects were dose-dependent. Moreover, the Hep-2 cells cultured with 50 micromol/L and 100 micromol/L Celecoxib showed obvious apoptosis, with the nuclear DNA of cells exhibiting characteristic DNA ladder. So Sc-58125 could inhibit the proliferation of Hep-2 cells by altering the G2 phase cells. However, Celecoxib had the same effect by changing the G1 phase cells and inducing apoptosis at higher concentration.
Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Dose-Response Relationship, Drug ; Laryngeal Neoplasms/*pathology ; Pyrazoles/*pharmacology ; Sulfonamides/*pharmacology ; Tumor Cells, Cultured

This study was aimed to investigate the effect of COX-2 inhibitor celecoxib on proliferation, apoptosis of human acute myeloid leukemia cell line HL-60 and its mechanism. HL-60 cells were cultured with different concentrations of celecoxib for 24 h. Cell proliferation was analyzed by CCK-8 assay, cell apoptosis and cell cycle distribution were detected by flow cytometry. Cyclin D1, cyclin E1 and COX-2 mRNA expressions were determined by RT-PCR. The results showed that after the HL-60 cells were treated with different concentrations of celecoxib for 24 h, the cell growth was significantly inhibited in a dose-dependent manner(r = 0.955), IC50 was 63.037 µmol/L of celecoxib. Celecoxib could effectively induce apoptosis in HL-60 cells also in dose-dependent manner(r = 0.988), blocked the HL-60 cells in the G0/G1 phase. The expression of cyclin D1, cyclin E1 and COX-2 mRNA were downregulated. It is concluded that celecoxib can inhibit the proliferation of HL-60 cells in dose-dependent manner, celecoxib causes cell G0/G1 arrest and induces cell apoptosis possibly through down-regulation of the cyclin D1 and cyclin E1 expression, and down-regulation of COX-2 expression respectively.
Apoptosis ; drug effects ; Celecoxib ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Gene Expression Regulation, Leukemic ; HL-60 Cells ; Humans ; Oncogene Proteins ; metabolism ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology