Abstract：
BACKGROUND AND PURPOSE:4-[3,5-Bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid CLEFMA is a new anti-cancer molecule. Here, we investigated changes in apoptosis and inflammatory markers during CLEFMA-induced tumour suppression. EXPERIMENTAL APPROACH:Lung adenocarcinoma H441 and A549, and normal lung fibroblast CCL151 cell lines were used, along with a xenograft model of H441 cells implanted in mice. Tumour tissues were analysed by immunoblotting, immunohistochemistry and/or biochemical assays. The ex vivo results were confirmed by performing selected assays in cultured cells. KEY RESULTS:CLEFMA-induced cell death was associated with cleavage of caspases 3/9 and PARP. In vivo, CLEFMA treatment resulted in a dose-dependent suppression of tumour growth and (18) F-fluorodeoxyglucose uptake in tumours, along with a reduction in the expression of the proliferation marker Ki-67. In tumour tissue homogenates, the anti-apoptotic markers (cellular inhibitor of apoptosis protein-1(cIAP1), Bcl-xL, Bcl-2, and survivin) were inhibited and the pro-apoptotic Bax and BID were up-regulated. Further, CLEFMA decreased translocation of phospho-p65-NF-κB into the nucleus. In vitro, it inhibited the DNA-binding and transcriptional activity of NF-κB. It also reduced the expression of COX-2 in tumours and significantly depressed serum TNF-α and IL-6 levels. These effects of CLEFMA were accompanied by a reduced transcription and/or translation of the invasion markers VEGF, MMP9, MMP10, Cyclin D1 and ICAM-1. CONCLUSIONS AND IMPLICATIONS:Overall, CLEFMA inhibited growth of lung cancer xenografts and this tumour suppression was associated with NF-κB-regulated anti-inflammatory and anti-metastatic effects.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Yadav VR,Sahoo K,Awasthi Vdoi
10.1111/bph.12406subject
Has Abstractpub_date
2013-12-01 00:00:00pages
1436-48issue
7eissn
0007-1188issn
1476-5381journal_volume
170pub_type
杂志文章abstract：:1. We studied the ability of nitric oxide (NO) to physiologically antagonize endothelin-1 (ET-1) induced constrictions in human internal mammary artery (IMA). We also investigated the hypothesis that NO interacts directly with ET-receptor binding in human heart and aorta. 2. ET-1 potently contracted IMA (EC(50) 6.86 n...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703834
更新日期：2001-01-01 00:00:00
abstract：:1. Tyrosine kinases have been proposed as regulators of voltage-operated calcium channels. The effects of a range of structurally different inhibitors of protein tyrosine kinases (PTK) were examined on voltage-operated calcium channel currents (I(Ba)) and pp60(c-src) kinase (c-src) activity in vitro. 2. I(Ba) was meas...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703186
更新日期：2000-04-01 00:00:00
abstract：:1. The effects of inhibiting endogenous Cu/Zn superoxide dismutase (SOD) with diethyldithiocarbamate (DETCA) were examined on the ability of hydroquinone, hydroxocobalamin and carboxy-PTIO to block nitrergic relaxation in the bovine retractor penis (BRP) muscle. 2. Incubation of strips of BRP with DETCA (3 mM) for 2 h...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15333.x
更新日期：1996-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Recently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning. EXPERIMENTAL APPROACH:The NMDA receptor antagonist 2-amino-5-phos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13070
更新日期：2015-05-01 00:00:00
abstract：:1 The binding of [3H]-muscimol, a potent gamma-aminobutyric acid (GABA) receptor agonist, to crude membrane preparations of bovine retina was studied, using a filtration method to isolate membrane-bound ligand. 2 Specific binding was found to be saturable and occurred at two binding sites with affinity constants of 4....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10934.x
更新日期：1980-01-01 00:00:00
abstract：:I.c.v. self-administration of MDMA (0.01-2 micro g per infusion), alone and in combination with CP 55,940 (0.4 micro g infusion(-1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704825
更新日期：2002-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Glucocorticoids appear to control Na⁺ absorption in pulmonary epithelial cells via a mechanism dependent upon serum and glucocorticoid-inducible kinase 1 (SGK1), a kinase that allows control over the surface abundance of epithelial Na⁺ channel subunits (α-, β- and γ-ENaC). However, not all data s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01860.x
更新日期：2012-06-01 00:00:00
abstract：:1 The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT), [3H]-haloperidol and [3H]-dopamine to human blood platelets was investigated and the effects of unlabelled haloperidol on [3H]-5-HT binding and (+)- and (-)-butaclamol on [3H]-haloperidol were studied. 2 Scatchard analysis did not show any specific binding of [3H]...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07812.x
更新日期：1978-07-01 00:00:00
abstract：:1 The effect of methylene, thio, and imido substituted analogues of adenosine 5'-triphosphate (ATP) on surfactant phospholipid secretion and calcium mobilization in rat isolated alveolar Type II cells was studied. 2 ATP was the most potent secretagogue of adenine nucleotides studied. The rank order of agonist potency ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11282.x
更新日期：1987-08-01 00:00:00
abstract：:1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15779.x
更新日期：1996-11-01 00:00:00
abstract：:1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704260
更新日期：2001-09-01 00:00:00
abstract：:1. The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702442
更新日期：1999-03-01 00:00:00
abstract：:Using a rat model which allows serial blood sampling and concurrent brain microdialysis sampling, we have investigated the temporal kinetic inter-relationship of levetiracetam in serum and brain extracellular fluid (frontal cortex and hippocampus) following systemic administration of levetiracetam, a new antiepileptic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704141
更新日期：2001-07-01 00:00:00
abstract：:1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700885
更新日期：1997-01-01 00:00:00
abstract：:1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and human isolated colon. 2 The aim of this study was to characterise Y(2) receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705298
更新日期：2003-06-01 00:00:00
abstract：:1. The effect of the calcitonin gene-related peptide antagonist (CGRP8-37, 400 nmol kg-1, i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2. The saphenous ner...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13878.x
更新日期：1993-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pyrazole derivatives have recently been suggested as selective blockers of transient receptor potential cation (TRPC) channels but their ability to distinguish between the TRPC and Orai pore complexes is ill-defined. This study was designed to characterize a series of pyrazole derivatives in term...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02126.x
更新日期：2012-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12005
更新日期：2013-02-01 00:00:00
abstract：:1 Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow. 2 Metiamide, in doses which inhibited pentagastrin-stimulated acid secretion, produced no increase in gastric ac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07361.x
更新日期：1975-02-01 00:00:00
abstract：:1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) cau...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703691
更新日期：2000-11-01 00:00:00
abstract：:1. The action of substance P (SP) on the release of gamma-aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea-pig urinary bladder. Substance P induced a dose-dependent contraction of strips of guinea-pig urinary bladder (EC50 = 1.2 x 10(-9) M). This contraction was ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12615.x
更新日期：1989-10-01 00:00:00
abstract：:1. The serine/threonine protein phosphatase (PP) inhibitors, okadaic acid and calyculin, attenuated the IgE-mediated release of histamine from human lung mast cells (HLMC) and basophils in a dose-dependent manner whereas an alternative PP inhibitor, microcystin, was ineffective. Calyculin was more potent than okadaic ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702169
更新日期：1998-11-01 00:00:00
abstract：:Nebivolol, a selective beta-adrenoceptor (beta1-AR) antagonist, induces vasodilatation by an endothelium- and NO-cGMP-dependent pathway. However, the mechanisms involved in the vascular effect of nebivolol have not been established. Thus, we evaluated the role of alpha1 and beta3-ARs in nebivolol-induced vasodilatatio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706648
更新日期：2006-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Biased GPCR ligands are able to engage with their target receptor in a manner that preferentially activates distinct downstream signalling and offers potential for next generation therapeutics. However, accurate quantification of ligand bias in vitro is complex, and current best practice is not a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13441
更新日期：2016-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. EXPERIMENTAL APPROACH:The following models of inflammation were employed: carrageenan-induced acute oedema (measured...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00244.x
更新日期：2009-10-01 00:00:00
abstract：:1. Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and composition are me...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701028
更新日期：1997-04-01 00:00:00
abstract：:1. The potencies of some beta-adrenoreceptor blocking drugs in reducing noradrenaline uptake by the isolated heart were compared with their potencies in reducing the release of noradrenaline from the heart by tyramine.2. Of the drugs tested, propranolol, pronethalol and dichloroisoprenaline were the most potent in blo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1968.tb07957.x
更新日期：1968-09-01 00:00:00
abstract：:Association between staphylococcal infection and pathogenesis of upper airways disease has been reported. This study aimed to investigate the mechanisms underlying the rat pulmonary inflammation induced by airway exposure to staphylococcal enterotoxin A (SEA). SEA (0.3-10 ng trachea(-1)) caused dose-dependent neutroph...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706393
更新日期：2005-11-01 00:00:00
abstract：:Schizophrenia remains an elusive multifaceted disorder with all evidence of its onset and aetiology pointing to a complex interplay of genetic, nutritional, environmental and developmental factors. Although several molecular and structural abnormalities have been reported for schizophrenia, no diagnostic test or other...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707658
更新日期：2008-03-01 00:00:00
abstract：:1. The effect of adenosine A1-receptor and P2-purinoceptor agonists on [3H]-inositol phosphate accumulation has been investigated in CHO-K1 cells transfected with the human adenosine A1-receptor. 2. Adenosine receptor agonists stimulated [3H]-inositol phosphate accumulation in CHO-K1 cells with a rank potency order of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16632.x
更新日期：1995-08-01 00:00:00
