Supplementary Table 1 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces <i>Cyclooxygenase-2</i> Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells
Kara MitchellKimberly B. SvensonWhitney LongmateKaterina GkirtzimanakiRafał SądejXianhui WangJihe ZhaoAristides G. EliopoulosFedor BerditchevskiC. Michael DiPersio
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Supplementary Table 1 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces <i>Cyclooxygenase-2</i> Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial CellsCite
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In this study we investigated expression of the two isoforms of the prostaglandin-forming enzyme, cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2), in sheep embryos. Using Western blot and immunohistochemical analyses, we demonstrated that Cox-2 was highly expressed in embryos from Day 8 to Day 17 of development whereas Cox-1 was undetectable during this time. The expression of Cox-2 was developmentally regulated. It was maximal between Days 14 and 16. There was a 30-fold increase in Cox-2 content per protein extract between Day 10 and Day 14, corresponding to a 50 000-fold increase in the whole embryo. The expression of Cox-2 declined after Day 16 to become undetectable by Day 25 of pregnancy. Cox-2 was localized in the trophoblastic cells and was not detected in the inner cell mass. The [3H]arachidonic acid metabolites synthesized by Cox-2-rich conceptuses were analyzed by HPLC after short-term embryo culture. Day 14 conceptuses released mainly cyclooxygenase metabolites and to a lesser extent lipoxygenase derivatives. Cyclooxygenase products were 6-keto-prostaglandin (PGF)lα, 18.2% (± 4.2), thromboxane-B2 22.51% (± 15.9), PGF2α. 21% (± 11), PGE2 14.5% (± 7.4), and PGD2 2.7% (± 2.6). Taken together, these results suggest an important role for the Cox-2- dependent cyclooxygenase metabolites during embryo development.
Prostaglandin H2
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Purpose:The anti-inflammatory effects of 1,8-cineole (eucalyptol) in the treatment of acute bronchitis and treatment of chronic airway diseases like asthma as well as hay fever have been observed in clinical practice for some time.The anti-inflammatory effect has been proven in numerous studies. Material and methods:The effect of 1,8-cineole on the activity of cyclooxygenase and its two isoforms (COX-1 and COX-2) were analysed and compared with the effects of indomethacin and celecoxib. Results:The ratio between the concentrations required to achieve 50% inhibition of COX-1 and COX-2 isoform activity was found to be 73.5.Discussion: For indomethacin, the ratio is 9.71 and for celecoxib 79.5.For indomethacin, it is about 10 times less than that of 1,8-cineole. Conclusion:The present study provides useful data suggesting that 1,8-cineole is a specific COX-2 blocker.
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Valdecoxib
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Stilbenes contained in various foods are associated with health beneficial effects. In this study six natural and one synthetic stilbene were tested for their potential to regulate the activity of lipoxygenase and cyclooxygenase in vitro. The most potent inhibitor of 5-lipoxygenase was pterostilbene (IC50 = 9.32 μM), whereas the strongest inhibitor of cyclooxygenase-1 and cyclooxygenase-2 was pinostilbene (IC50s = 1.90 and 0.35 μM, respectively). Pterostilbene (IC50s = 11.70 and 27.04 μM for cyclooxygenase-1 and cyclooxygenase-2, respectively) and oxyresveratrol (IC50s = 18.49; 2.79 and 14.71 μM for 5-lipoxygenase, cyclooxygenase-1, and cyclooxygenase-2, respectively) were capable to inhibit catalytic activity of all three tested enzymes. Isorhapontigenin (IC50s = 8.81 and 24.00 μM for cyclooxygenase-1 and cyclooxygenase-2, respectively) and rhapontigenin (IC50s = 24.55 and 36.12 μM for cyclooxygenase-1 and cyclooxygenase-2, respectively) were only moderate or weak inhibitors of both cyclooxygenase forms. In summary, these results indicated that besides the known cyclooxygenase inhibitor resveratrol also other natural stilbenes could be potent inhibitors of the arachidonic acid pathway and deserve further attention as compounds with promising health benefits.
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The enzyme, cyclooxygenase is now well recognized to exist in two isoforms i.e. cyclooxygenase-1 and cyclooxygenase-2. Cyclooxygenase-1 is constitutively expressed serving the so-called 'house-keeping' role while, cyclooxygenase-2 was thought to be expressed in pathophysiological conditions such as inflammation. It is now known that cyclooxygenase-2 plays a key role in a wide range of physiological processes. In the current article the multifaceted profile of cyclooxygenase-2 enzyme in th'e body is described indicating its potential clinical and diagnostic applications. It is also discussed how the currently available selective cyclooxygenase-2 inhibitors can affect the normal physiological role of cyclooxygenase-2 enzyme.
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In rats, neither the cyclooxygenase-1 inhibitor SC-560 nor the cyclooxygenase-2 inhibitor rofecoxib damages the gastric mucosa. Coadministration of dexamethasone induced injury in SC-560- but not in rofecoxib-treated rats. High levels of cyclooxygenase-1 protein occurred in the gastric mucosa of control rats, with no change after administration of SC-560. In contrast, the gastric cyclooxygenase-2 protein levels were low in control rats, but increased in a time-dependent manner after administration of SC-560. Dexamethasone prevented the increase in cyclooxygenase-2 protein levels. Our findings show that inhibition of cyclooxygenase-1 upregulates cyclooxygenase-2. When the upregulation is prevented by dexamethasone, gastric damage develops, suggesting that induction of cyclooxygenase-2 represents a compensatory mechanism that counteracts the injurious effect of cyclooxygenase-1 inhibition.
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