Search results for "anti-inflammatory agents"
showing 10 items of 576 documents
Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells
2013
The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1 h of incubation with 25 µM PN and reached a peak at 8-16 h. This effect seemed to be a consequence of ROS production, because N-acetylcystein…
The oxygen radicals involved in the toxicity induced by parthenolide in MDA-MB-231 cells
2014
It has been shown that the sesquiterpene lactone parthenolide lowers the viability of MDA-MB-231 breast cancer cells, in correlation with oxidative stress. The present report examined the different radical species produced during parthenolide treatment and their possible role in the toxicity caused by the drug. Time course experiments showed that in the first phase of treatment (0-8 h), and in particular in the first 3 h, parthenolide induced dichlorofluorescein (DCF) signal in a large percentage of cells, while dihydroethidium (DHE) signal was not stimulated. Since the effect on DCF signal was suppressed by apocynin and diphenyleneiodonium (DPI), two inhibitors of NADPH oxidase (NOX), we s…
Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.
2012
Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A 4 is an endogenous allosteric enhancer of the CB 1 cannabinoid receptor. Lipoxin A 4 was detected in brain tissues, did not compete for the orthosteric binding site of the CB 1 receptor (vs. 3 H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating …
Cyclooxygenases in hepatocellular carcinoma
2006
Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs non-selectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by pro-inflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpr…
Induction of apoptosis and inhibition of cell growth in human hepatocellular carcinoma cells by COX-2 inhibitors
2005
The aim of the present study was to examine the effects of nonselective (indomethacin) and selective cyclooxygenase-2 (COX-2) inhibitors (NS-398, nimesulide, and CAY10404) on cell growth, cell cycle distribution, and apoptosis in three human hepatocellular carcinoma cell lines (HepG2, HuH-6, and HA22T/VGH) with different characteristics of differentiation and biological behavior. The four COX inhibitors showed a dose-dependent growth-inhibitory effect in all the cell lines. No substantial arrests in the progression of the cells through the cell cycle were observed after treatment of HuH-6 or HA22T/VGH for 48 h with the various inhibitors. On the other hand, there were significant increases …
The influence of atorvastatin on parameters of inflammation left ventricular function, hospitalizations and mortality in patients with dilated cardio…
2013
Background: We assessed the influence of atorvastatin on selected indicators of an inflammatory condition, left ventricular function, hospitalizations and mortality in patients with dilated cardiomyopathy (DCM). Methods. We included 68 DCM patients with left ventricular ejection fraction (LVEF) ≤40% treated optimally in a prospective, randomized study. They were observed for 5 years. Patients were divided into two groups: patients who were commenced on atorvastatin 40 mg daily for two months followed by an individually matched dose of 10 or 20 mg/day (group A), and patients who were treated according to current recommendations without statin therapy (group B). Results: After 5-year follow-u…
Atrial natriuretic factor, but not oxytocin, is present in atherosclerotic plaques of human common carotid arteries
2010
We performed a study on 25 common carotid arteries (CCA) affected by atherosclerotic plaques, comparing them to 25 normal CCA. We researched the presence and localisation of atrial natriuretic factor (ANF) and oxytocin (OX) by immunohistochemistry. We found ANF abundantly expressed in plaques, mainly localising in intima and subintima layers; by contrast normal vessels were scarcely positive or negative; finally, OX resulted negative or weakly positive in both atherosclerotic and normal vessels. Our results show for the first time ANF presence in atherosclerotic plaques of CCA and are in agreement with other studies, mainly performed in vitro, that hypothesise the involvement of this molecu…
Regulation of the inflammatory response by tin protoporphyrin IX in the rat anterior cruciate ligament transection model of osteoarthritis
2010
The purpose of this study was to investigate several inflammatory mediators and cartilage degradation molecules as possible biomarkers of joint lesion in the anterior cruciate ligament transection (ACLT) model of osteoarthritis in rats. We also assessed whether the treatment with the anti-inflammatory agent tin protoporphyrin IX (SnPP) reduces the progression of disease. Our results indicate that serum levels of interleukin (IL)-6 and PGE2 are significantly increased in ACLT rats 10 weeks after surgery, whereas the increases in IL-1β and tumor necrosis-α were not significant. In addition, our data suggest that IL-17 is the main pro-inflammatory cytokine in the ACLT joint. We have shown that…
Transcriptional and post-transcriptional regulation of iNOS expression in human chondrocytes
2009
Chondrocytes are important for the development and maintenance of articular cartilage. However, both in osteoarthritis (OA) and rheumatoid arthritis (RA) chondrocytes are involved in the process of cartilage degradation and synthesize important immunomodulatory mediators, including nitric oxide (NO) generated by the inducible NO synthase (iNOS). To uncover the role of iNOS in the pathomechanisms of OA and RA, we analyzed the regulation of iNOS expression using immortalized human chondrocytes as a reproducible model. In C-28/I2 chondrocytes, iNOS expression was associated with the expression of the chondrocyte phenotype. Peak induction by a cytokine cocktail occurred between 6 and 8h and dec…
Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42
2005
Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…