Abstract：
:To uncover the full spectrum of its pharmacological activities, the selective COX-2 inhibitor celecoxib is routinely being used at concentrations of up to 100 microM in cell culture. At these elevated concentrations, several COX-2-independent effects were identified, although many details of these events have remained unclear. Here, we report a COX-2-independent effect of celecoxib that might have profound consequences for the interpretation of previous results obtained at elevated concentrations of this drug in vitro. We found that celecoxib rapidly inhibits general protein translation at concentrations as low as 30 microM. This appears to be a consequence of endoplasmic reticulum (ER) stress and entails the phosphorylation and inactivation of eukaryotic translation initiation factor 2 alpha (eIF2alpha). These effects were not achieved by other coxibs (rofecoxib, valdecoxib) or traditional NSAIDs (indomethacin, flurbiprofen), but were mimicked by the COX-2-inactive celecoxib analog, 2,5-dimethyl-celecoxib (DMC), indicating COX-2 independence. Considering the obvious impact of blocked translation on cellular function, we provide evidence that this severe inhibition of protein synthesis might suffice to explain some of the previously reported COX-2-independent effects of celecoxib, such as the down-regulation of the essential cell cycle regulatory protein cyclin D, which is a short-lived protein that rapidly disappears in response to the inhibition of protein synthesis. Taken together, our findings establish ER stress-induced inhibition of general translation as a critical outcome of celecoxib treatment in vitro, and suggest that this effect needs to be considered when interpreting observations from the use of this drug in cell culture.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Pyrko P,Kardosh A,Schönthal AHdoi
10.1016/j.bcp.2007.08.029subject
Has Abstractpub_date
2008-01-15 00:00:00pages
395-404issue
2eissn
0006-2952issn
1873-2968pii
S0006-2952(07)00590-4journal_volume
75pub_type
杂志文章abstract：:Mercaptomethylimidazole (MMI), a potent antithyroid drug of the thionamide group, induces both acid and pepsinogen secretion independently in control and pylorus ligated mice. The effect is dose dependent and the drug is more effective than histamine, carbachol or isoproterenol when administered by an intraperitoneal ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90498-a
更新日期：1990-09-01 00:00:00
abstract：:Tanshinone I (Tanshinone-1), a major active principle of the traditional Chinese medicine Salvia miltiorrhiza, possesses excellent anticancer properties, including inhibiting proliferation, angiogenesis and metastasis and overcoming multidrug resistance (MDR). However, its direct anticancer molecular target(s) remain ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2018.05.006
更新日期：2018-08-01 00:00:00
abstract：:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial membrane hyperplasia, infiltration of inflammatory cells and bone tissue destruction. Although there have been many measures taken for RA therapy in recent years, they are not sufficiently safe or effective. Thus, it is very i...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114360
更新日期：2021-01-01 00:00:00
abstract：:The differentiation-inducing factor-1 (DIF-1) is a lipophilic signal molecule (chlorinated alkylphenone) that induces stalk-cell differentiation in the cellular slime mould Dictyostelium discoideum. It has also been shown that DIF-1 and its derivative (DIF-3) suppress cell growth in mammalian tumor cells. In the prese...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.06.002
更新日期：2005-09-01 00:00:00
abstract：:High concentrations of non steroidal antiinflammatory drugs (NSAIDs) exert preventive effects against carcinogenesis. Their molecular mechanism of action remains to be elucidated. Based on previous reports with salicylate, we have made the hypothesis that various NSAIDs can activate the mitogen-activated protein kinas...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00826-7
更新日期：2002-01-15 00:00:00
abstract：:The activity of tyrosine hydroxylase (TH) in the corpus striatum of haloperidol treated and control rats has been examined. The activation of TH by haloperidol caused a decrease in the Km for tetrahydrobiopterin but no change in the Vmax. This effect was totally abolished when homogenates were prepared at high values ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90364-7
更新日期：1983-11-15 00:00:00
abstract：:Peroxidase (EC 1.11.1.7)/H2O2, ceruloplasmin (human type X)/O2, and tyrosinase (EC 1.14.18.1)/O2 all oxidized the indolic neurotransmitter 5-hydroxytryptamine (5-HT) in the physiological pH domain. Peroxidase/H2O2 oxidized 5-HT at pH values down to about 2.5. All oxidation reactions generated complex mixtures of produ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90653-m
更新日期：1991-04-15 00:00:00
abstract：:Cancer develops through a series of genetic changes leading to malignant transformation. Numerous gene and pathways involved in stages of progression to frank malignancy have been elucidated. These genetic changes result in aberrations in fundamental cellular processes controlling proliferation, apoptosis, differentia...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.03.004
更新日期：2006-08-28 00:00:00
abstract：:The inhibitory effects of quinolone antimicrobial agents and nonsteroidal anti-inflammatory drugs on purified mouse liver mitochondrial medium chain acyl-CoA synthetase catalyzing the first reaction of glycine conjugation were examined, using hexanoic acid as a substrate. Enoxacin, ofloxacin, nalidixic acid, diflunisa...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00667-0
更新日期：2001-08-01 00:00:00
abstract：:Hepatic microsomal preparations from male and female rats were delipidated by column chromatography following cholate solubilisation. The enzyme activities were reconstituted using known lipids and the vesicle reconstitution method. Enzyme activity was assayed using lignocaine as the substrate for the mixed function o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90071-2
更新日期：1987-04-15 00:00:00
abstract：:Purification of functional nucleoside transporters has been hampered by the instability of detergent-solubilized proteins. The present study was undertaken to determine if the presence of specific transporter ligands in the solubilization medium could enhance the functional stability of the isolated proteins. Ehrlich ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00857-x
更新日期：1997-03-07 00:00:00
abstract：:(-)-2'-deoxy-3'-thiacytidine (3TC) has been shown to be a potent, selective inhibitor of HIV replication in vitro, which requires phosphorylation to its 5'-triphosphate for antiviral activity. The intracellular concentration of 3TC 5'-triphosphate in phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes (P...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)96620-a
更新日期：1995-09-28 00:00:00
abstract：:Resealed synaptic plasma membrane vesicles exhibit Na+-dependent Ca2+ transport activity which may participate in regulation of free Ca2+ concentrations in nerve endings. Sodium chloride-loaded vesicles took up Ca2+ from the external medium (150 mM KCl-25 mM Tris/HCl) in the presence of an outward-directed Na+ gradien...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90612-3
更新日期：1983-03-15 00:00:00
abstract：:In this study we analyse the effects of the anti-tumor compound distamycin on the binding of nuclear factor(s) to a synthetic oligonucleotide (GTATA/IFN-gamma) mimicking a putative regulatory region of the human HLA-DR alpha gene. This region contains the sequence (GTATA), that is required for nuclear protein binding ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90620-k
更新日期：1991-02-15 00:00:00
abstract：:The signal transducer and activator of transcription 3 is a constitutively activated oncogenic protein in various human tumors and represents a valid target for anticancer drug design. In this study, we have achieved a new type of STAT3 inhibitors based on structural modifications on shikonin scaffold, guided by compu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.10.009
更新日期：2017-12-15 00:00:00
abstract：:The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90540-y
更新日期：1992-10-06 00:00:00
abstract：:A comparative study of the N-B transition and the drug binding properties of human serum albumin samples from various sources has been carried out with the help of circular dichroism and equilibrium dialysis. It was found that when warfarin was used as a marker the midpoint pH and the cooperative nature of the N-B tra...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90293-3
更新日期：1982-12-01 00:00:00
abstract：:The serine esterase inhibitor diisopropyl fluorophosphate (DFP) had been reported previously to inhibit IgE-dependent histamine release. Recently, it has been demonstrated that lower concentrations of DFP enhance IgE-dependent histamine release and inhibit desensitization. This manuscript describes the abilities of se...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90686-6
更新日期：1986-12-01 00:00:00
abstract：:Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to periph...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.05.025
更新日期：2004-08-15 00:00:00
abstract：:α6β2-Containing nicotinic acetylcholine receptors (α6β2* nAChRs) are predominantly expressed in midbrain dopaminergic neurons, including substantia nigra pars compacta (SNc) neurons and their projections to striatal regions, where they regulate dopamine release and nigrostriatal activity. It is well established that n...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113788
更新日期：2020-04-01 00:00:00
abstract：:Rational approaches to targeted cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportuniti...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2010.03.001
更新日期：2010-09-01 00:00:00
abstract：:We investigated the effects of tranilast on inducible cyclooxygenase (COX2)-mediated prostaglandin E2 (PGE2) production and enzyme induction in interleukin-lbeta (IL-1beta)-stimulated cultured dermal fibroblasts. IL-1beta enhanced PGE2 production in cultured fibroblasts. Tranilast did not affect constitutive cyclooxyg...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00187-1
更新日期：1997-06-15 00:00:00
abstract：:The binding of nimodipine, a 1,4-dihydropyridine Ca2+ channel antagonist, and of Bay K 8644, a Ca2+ channel activator, was measured in several regions of rat brain and compared to the distribution of K+ depolarization-induced 45Ca2+ uptake into synaptosomes. The maximum binding densities (Bmax) of [3H]nimodipine and [...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90575-2
更新日期：1987-12-01 00:00:00
abstract：:After rats were injected with the reduced glutathione (GSH) depletor phorone (diisopropylidene acetone, 250 mg/kg, i.p.), there was a significant increase in microsomal glutathione S-transferase activity in the liver. The maximum activity was observed 24 hr after injection and was about 2-fold that of the control acti...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90216-9
更新日期：1986-02-01 00:00:00
abstract：:The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufural...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90573-9
更新日期：1987-12-01 00:00:00
abstract：:The present investigation addressed the role of verapamil for oral pharmacokinetics of morphine-6-beta-glucuronide (M6G). Male Sprague-Dawley rats received 62.5 mg kg(-1) M6G-dihydrate orally w/wo pre-treatment with 70 mg kg(-1) verapamil. Intravenous M6G (3.9 mg kg(-1) ) and oral morphine (52.7 mg kg(-1) morphine-hyd...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00881-x
更新日期：2002-04-15 00:00:00
abstract：:Structurally diverse chemotherapeutic and chemopreventive drugs, including camptothecin, doxorubicin, sanguinarine, and others, were found to cause covalent crosslinking of proliferating cell nuclear antigen (PCNA) trimers in mammalian cells exposed to fluorescent light. This PCNA damage was caused by both nuclear and...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.09.003
更新日期：2008-12-15 00:00:00
abstract：:Multiple molecular forms of cyclic nucleotide phosphodiesterase have been characterized in various tissues and cells according to their substrate specificity, intracellular location, and calmodulin dependence. The purpose of this study was to evaluate the possible involvement of different molecular forms of phosphodie...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90304-4
更新日期：1990-08-15 00:00:00
abstract：:Hepatic fibrosis is characterized by excess type I collagen deposition and exacerbated inflammatory response. Naltrexone, an opioid receptor antagonist used for treating alcohol abuse, attenuates hepatocellular injury in fibrotic animal models, which can be accompanied by deleterious side effects. Additionally, opioid...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.01.015
更新日期：2011-04-15 00:00:00
abstract：:The beta 2-adrenoceptor agonist, clenbuterol (initially 5 mg/kg), was found to significantly reduce plasma tyrosine and raise brain tryptophan levels (P less than 0.01). By comparison, decreases in plasma tryptophan and increases in brain tyrosine were small and often nonsignificant. Amino acid levels measured in diff...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90003-8
更新日期：1989-09-15 00:00:00
