scholarly journals Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2

2010 ◽  
Vol 24 (1) ◽  
Author(s):  
Takaoka
1999 ◽  
Vol 112 (18) ◽  
pp. 3147-3155
Author(s):  
N.A. Callejas ◽  
M. Casado ◽  
L. Bosca ◽  
P. Martin-Sanz

Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappaB) since proteasome inhibitors and antioxidants that abrogated NF-kappaB activity suppressed the induction of both genes. The time-dependent fall of the mRNA levels of NOS-2 and COX-2 paralleled the inhibition of NF-kappaB, determined by electrophoretic mobility shift assays, and the increase of the IkappaBalpha and IkappaBbeta inhibitory proteins. Isolated trophoblasts synthesized reactive oxygen intermediates (ROI), a process impaired after culturing the cells, and that might be involved in the NF-kappaB activation process. Moreover, treatment of recently isolated cells with ROI scavengers suppressed the expression of COX-2 and NOS-2. Challenge of trophoblasts with interleukin-1beta up-regulated the expression of both proteins, an effect that was potentiated by lipopolysaccharide. These results indicate that the physiological expression of NOS-2 and COX-2 in trophoblasts involves a sustained activation of NF-kappaB which inhibition abrogates the inducibility of both genes.


2011 ◽  
Vol 29 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Hye-Jeong Park ◽  
Hyung-Sun Youn

Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-κB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense.


2021 ◽  
Author(s):  
Anuradha Kalita ◽  
MANAS DAS ◽  
Bhabajyoti Das ◽  
Momita Rani Baro

Abstract Garcinia is a tropical plant that has been traditionally used in medicinal folklore for its potential antioxidant, antibacterial, anti-hyperlipidemic, anti-diabetic, hepatoprotective, etc. In this study, Garcinia herbal extract (GHE) and one of its important phytocompound (garcinol) were evaluated for their inhibitory action against important inflammatory markers inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. iNOS and COX-2 plays an major role in the process of inflammation and inhibition of these molecules will help to alleviate the inflammatory process. The cells were pre-treated with two doses of Garcinia (230µg/ml and 115µg/ml); garcinol (12µM and 6µM) followed by stimulation with 1µg/ml of LPS for 24h. The results of the study demonstrated that GHE and garcinol plays an important role in suppressing LPS- induced relative mRNA expression of iNOS, COX-2 and subsequent reduction in the levels of nitric oxide and prostaglandin E 2 . Molecular docking analysis of garcinol and hydroxycitric acid, the major active components of GHE with iNOS and COX-2 proteins showed potent interaction with low binding energies. This study suggests that GHE (containing high percentage of HCA) and garcinol may possess anti-inflammatory activity thus providing a possibility for drug designing as iNOS and COX-2 inhibitors.


2010 ◽  
Vol 48 (6) ◽  
pp. 1125-1133 ◽  
Author(s):  
M. Kommareddy ◽  
R. M. McAllister ◽  
V. K. Ganjam ◽  
J. R. Turk ◽  
M. Harold Laughlin

The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with NG-nitro-l-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant ( P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.


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