Search results for " Non-Steroidal"
showing 10 items of 281 documents
Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
2011
Cancers are the largest cause of mortality and morbidity in industrialized countries. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of carcinogenesis processes and associated inflammatory effects such as the modulation of innate immune cells and adaptive immune cells that could infiltrate the tumor. In the tumor microenvironment, there is a delicate balance between antitumor immunity and tumor-originated proinflammatory activity, which weaken antitumor immunity. Consequently; modulation of immune cells and inflammatory processes represent attractive targets for therapeutic intervention in malignant diseases with the goal to restore the sensiti…
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…
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…
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…
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…
Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line
2001
We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA …
Presenilin is the molecular target of acidic γ-secretase modulators in living cells.
2012
The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain an…