Abstract：
:The correlation between the Phosphoinositide 3-kinase (PI3K) axis and crucial mechanisms involved in the maintenance of the neoplastic nature of multiple myeloma (MM) has recently evolved a general agreement that PI3K inhibition-based therapies could construct an exciting perspective for the future treatment strategies. Our results outlined that abrogation of PI3K using pan-PI3K inhibitor BKM120 decreased survival of MM cells through induction of a caspase-3-dependent apoptosis coupled with SIRT1-mediated G2/M arrest in both KMM-1 and RPMI 8226 cell lines; however, the cell responses to the inhibitor was quite different, introducing wild-type PTEN-expressing RPMI 8226 as less sensitive cells. By investigating the sensitivity extent of a panel of hematological cell lines to BKM120, we found no significant association with respect to PTEN status. As far as we are aware, the results of the present study propose for the first time that the inhibitory effect of BKM120 was overshadowed, at least partially, through over-expression of either c-Myc or nuclear factor (NF)-κB in less sensitive MM cells. While there was no significant effect of the inhibitor on the expression of c-Myc in RPMI 8226, we found an enhanced cytotoxic effect when BKM120 was used in combination with a small molecule inhibitor of c-Myc. Noteworthy, the results of the synergistic experiments also revealed that BKM120 could produce a synergistic anti-cancer effect with carfilzomib (CFZ) and provided an enhanced therapeutic efficacy in MM cells, highlighting that PI3K inhibition might be a befitting approach in MM both in mono and combined therapy.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Safaroghli-Azar A,Bashash D,Kazemi A,Pourbagheri-Sigaroodi A,Momeny Mdoi
10.1016/j.ejphar.2018.10.036subject
Has Abstractpub_date
2019-01-05 00:00:00pages
89-98eissn
0014-2999issn
1879-0712pii
S0014-2999(18)30621-6journal_volume
842pub_type
杂志文章abstract：:Isolated rat mast cells were used to study whether ionophore A23187 could induce histamine release by mobilizing cellular calcium. The histamine release was a slow process which was completed after about 20 min incubation with A23187. The A23187-induced histamine release was inhibited after incubation of the cells wit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90100-4
更新日期：1980-04-04 00:00:00
abstract：:Eosinophils and their granular proteins are crucial for combating allergic airway diseases. Eosinophils derived from HL-60 clone 15 (HC15) cells have been established as a feasible alternative cell model for human primary eosinophils. Simvastatin, a cholesterol-lowering agent, has been shown to exhibit anti-inflammato...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.05.029
更新日期：2019-08-05 00:00:00
abstract：:Anti-tumor activity of bakuchiol, an analogue of resveratrol, was investigated on human lung adenocarcinoma A549 cell line. MTT assay revealed that IC(50) of bakuchiol at 72h was 9.58+/-1.12 micromol/l, much lower than that of resveratrol (33.02+/-2.35 micromol/l). Bakuchiol but not resveratrol elevated intracellular ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.06.025
更新日期：2010-09-25 00:00:00
abstract：:It has been shown that galanin plays a role in central cardiovascular regulation. Galanin administered centrally induces an increase of heart rate and a weak vasodepressor response, whereas the N-terminal galanin fragment (1-15) elicits vasopressor effects and tachycardia. Furthermore, it has been shown that galanin-(...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00383-6
更新日期：2000-07-07 00:00:00
abstract：:The quaternary antagonist gallamine discriminates subpopulations of muscarinic receptors in the forebrain and brainstem of the rat and also modulates the binding of other muscarinic ligands via an allosteric mechanism in both brain regions. The calcium channel antagonist verapamil exhibits a similar allosteric effect ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90006-9
更新日期：1987-11-24 00:00:00
abstract：:Severe depletion of 5-hydroxytryptamine (5-HT) by para-chlorophenylalanine (pCPA, 150 mg/kg per day x3) did not alter the hypophagic effect of d-fenfluramine (1-3 mg/kg i.p.) 1 h after food presentation in 24-h food-deprived rats, and moderately and comparably increased the hypophagic effects of its metabolite, d-norf...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90013-8
更新日期：1993-09-21 00:00:00
abstract：:The effect of adrenaline on the electrically evoked noradrenaline overflow in the portal vein of adrenal demedullated freely moving rats was studied. Adrenaline (100 ng/min) was infused for 2 h into the portal vein. After a 1-h interval when plasma adrenaline had returned to pre-infusion undetectable levels, the porta...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90185-k
更新日期：1993-10-26 00:00:00
abstract：:AY-22,241 (Actodigin) is a new rapid-acting semisynthetic cardiotonic steroid. In experiments on contractility of cat papillary muscle, Actodigin (2 times 10(-7) to 4 times 10(-6) M) produced a dose-dependent positive inotropic effect, a marked increase in the maximum rate of force development, and no change in restin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90316-7
更新日期：1975-05-01 00:00:00
abstract：:The characteristics of histamine H1-receptors on astrocytes from the cerebral cortex of newborn rats in primary culture were analyzed with a [3H]mepyramine binding assay, and compared with those in the cerebral cortex. The apparent dissociation constant (KD) of [3H]mepyramine binding, the apparent inhibition constants...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90007-1
更新日期：1989-11-28 00:00:00
abstract：:Cats, sedated and paralyzed, showed a significant increase in body temperature after intravenous injection of morphine while animals with additional spinal blockade (C3) from injection of 2% lidocaine solution, did not. The results suggest that motor activity is not necessary for morphine-induced hyperthermia in the c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90113-9
更新日期：1978-06-01 00:00:00
abstract：:Peptides based in the stabilised tetrapeptide HTyr-D-Ala-Gly-MePheOH have been synthesised and shown to have substantial opioid activity both in vitro and in vivo. The selectivity of these compounds of different receptor populations has been investigated using both isolated tissue assays and binding studies. Results s...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90364-2
更新日期：1981-04-09 00:00:00
abstract：:Glycine displaces [3H]CGP-39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) binding to the glutamate recognition site with both high and low affinity. We reported previously that chronic treatment with antidepressants reduced the proportion of high to low affinity sites, or, even eliminated the high af...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01589-6
更新日期：1998-01-26 00:00:00
abstract：:Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50 micrograms/mouse) accelerated the synthesis/turnover of 5-hydroxytryptamine (5-HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in mouse brain. These effects were completely antagonized by pretreatment with a glu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90782-y
更新日期：1992-10-06 00:00:00
abstract：:We have investigated the effects of substituting extracellular Na+ by choline or K+ on responses of quin2- and fura-2-loaded human platelets to thrombin and platelet-activating factor (PAF). Na+ substitution by choline did not affect the extent of the rise in [Ca2+]i evoked by either agonist. The response to thrombin,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90563-7
更新日期：1986-08-22 00:00:00
abstract：:The pharmacological properties of two angiotensin II analogues containing carboranylalanine (Car) are reported. Sar-Arg-Val-Tyr-Val-His-Pro-Car is a weak partial agonist showing 15% intrinsic activity and a very long lasting action, specific for the angiotensin II receptor of the rabbit aorta. Sar-Arg-Val-Car-Val-His-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90458-6
更新日期：1980-09-05 00:00:00
abstract：:Galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis and autophagy to suppress the proliferation of HepG2 cells. In this study, we demonstrated that galangin induced autophagy by increasing the ratio of AMP/TAN in HepG2 cells. It stimulated the pho...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.08.026
更新日期：2013-10-15 00:00:00
abstract：:Galantamine is a reversible inhibitor of acetylcholinesterase and an allosteric-potentiating ligand of the nicotinic acetylcholine receptors. It is used for treating mild-to-moderate Alzheimer's disease. Interestingly, QT interval prolongation on the electrocardiogram (ECG), malignant ventricular arrhythmias and synco...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.002
更新日期：2012-04-15 00:00:00
abstract：:Rat anococcygeus muscles were isolated 4 h after treatment with either E. coli endotoxin (20 mg kg-1 i.p.) or saline. The contractile responses of the muscle to electrical field stimulation, and to the alpha 1-adrenoceptor agonist cirazoline were impaired by endotoxin treatment. Inhibition of the L-arginine pathway wi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90285-x
更新日期：1991-09-24 00:00:00
abstract：:Here we investigated the effect of naloxone-precipitated morphine withdrawal on the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1 mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of morphine, induced an immediate increase in hippocampal noradrenaline releas...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90052-6
更新日期：1992-05-14 00:00:00
abstract：:The investigation examined the mechanism of the increase in brain tryptophan concentration of rats treated with d-amphetamine. Certain well recognised influences upon brain tryptophan have been excluded as responsible. Thus, the effect is not associated with changes in the plasma concentrations of NEFA or free tryptop...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90307-2
更新日期：1978-06-15 00:00:00
abstract：:To investigate cellular electrophysiologic alterations due to lipid peroxidation of the cell membrane by free radicals as a possible cause of coronary reperfusion arrhythmias, we studied the effects of t-butyl hydroperoxide on the spontaneous action potential and membrane currents of the rabbit sinoatrial and atrioven...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90027-6
更新日期：1995-03-16 00:00:00
abstract：:We have earlier shown that the glucagon-like peptide 1 receptor agonist exendin-4 stimulates neurogenesis in the subventricular zone and excerts anti-parkinsonian behavior. The aim of this study was to assess the effects of exendin-4 treatment on hippocampus-associated cognitive and mood-related behavior in adult rode...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.10.008
更新日期：2011-01-10 00:00:00
abstract：:Experiments were designed to examine some characteristics of an orally active antihypertensive agent, SGB-1534 on alpha-adrenoceptors in spinally anesthetized dogs. In the saphenous arterial bed perfused by a constant pump volume, saphenous nerve stimulation and bolus applications of norepinephrine and phenylephrine i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90579-0
更新日期：1986-11-19 00:00:00
abstract：:The inhibition of the tail-flick response induced by beta-endorphin given i.c.v. has been demonstrated to be mediated by the stimulation of epsilon- but not mu-, delta- or kappa-opioid receptors. beta-Endorphin given i.t. also inhibited the tail-flick response. The present studies were designed to determine what types...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90096-m
更新日期：1992-04-07 00:00:00
abstract：:The influence of GABA-ergic stimulation on the centrally evoked pressor and tachycardic responses to substance P (SP) was investigated in conscious rats. Intracerebroventricular (i.c.v.) pretreatment with the potent GABA agonist muscimol attenuated the pressor responses to i.c.v. administered SP in a dose-dependent an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90512-1
更新日期：1986-11-12 00:00:00
abstract：:Animal studies reveal that diverse environmental stimuli that generate anxiety-like behaviors also induce antinociception; conversely, clinical data show that pain perception is reduced under anxiolysis. This study was conducted to investigate the influence of pharmacologically induced-anxiety on nociception and antin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.06.060
更新日期：2006-10-10 00:00:00
abstract：:The role of the glutamate 'metabotropic' receptor was investigated in an experimental model of focal ischaemia-induced neurodegeneration. The metabotropic agonist, trans-1-amino cyclopentane-1,3-dicarboxylic acid (t-ACPD, 20 mg/kg i.p.), was administered to mice immediately after middle cerebral artery occlusion (MCAO...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90382-e
更新日期：1992-06-05 00:00:00
abstract：:σ2 Receptor subtype is overexpressed in a variety of human tumors, with σ2 agonists showing antiproliferative effects towards tumor cells through multiple pathways that depend both on the tumor cell type and on the molecule type. Therefore, σ2 receptor is an intriguing target for tumor diagnosis and treatment despite ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.03.067
更新日期：2015-07-05 00:00:00
abstract：:The pharmacological profile of YM358, 2,7-diethyl-5-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]tri azole potassium salt monohydrate, a novel non-peptide angiotensin AT1 receptor antagonist, was studied in vitro and in vivo. YM358 competed with [125I][Sar1, Ile8]angiotensin II for angiotensi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01189-8
更新日期：1997-09-24 00:00:00
abstract：:Major depression is a highly prevalent disorder and is predicted to be the second leading cause of disease burden by 2020. Although many antidepressant drugs are currently available, they are far from optimal. Approximately 50% of patients do not respond to initial first line antidepressant treatment, while approximat...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2014.07.046
更新日期：2015-04-15 00:00:00
