Abstract：
:A major limitation of cancer treatment is the ability of cancer cells to develop resistance to chemotherapeutic drugs, by the establishment of multidrug resistance. Here, we characterize MC70 as ABC transporters inhibitor and anticancer agent, alone or with chemotherapy. MC70 was analyzed for its interaction with ABCB1, ABCG2 and ABCC1 by specific transport assays. In breast and colon cancer cell lines, cell growth and apoptosis were measured by MTT assay and DNA laddering Elisa kit, respectively. Cell cycle perturbation and cellular targets modulation were analyzed by Flow-cytometry and Western blotting, respectively. MC70 interacted with ABC transporters. In breast cancer cells, MC70 slightly inhibited cell proliferation strongly enhancing doxorubicin effectiveness. By contrast, MC70 was found to inhibit cell growth in colon cancer cells without affecting doxorubicin efficacy and in combination with topoisomerase I inhibitors it could be a promising therapeutic approach. What is more, it was also observed that MC70 induced apoptosis, canceled in favor of necrosis when given in combination with high doses of doxorubicin. MC70 inhibited cell migration probably through its interaction with sigma-1 receptor. Modulations of i) cell cycle, ii) pAkt and the phosphorylation of the three MAPKs were highlighted, while any activity was excluded at transcription level, thus accounting for the phenotypic effects observed. MC70 might be considered as a new potential anticancer agent capable to i) enhance chemotherapy effectiveness and ii) to play a contributory role in the treatment of chemotherapy resistant tumors.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Azzariti A,Quatrale AE,Porcelli L,Colabufo NA,Cantore M,Cassano G,Gasparre G,Iannelli G,Tommasi S,Panaro MA,Paradiso Adoi
10.1016/j.ejphar.2011.08.025subject
Has Abstractpub_date
2011-11-16 00:00:00pages
74-84issue
1eissn
0014-2999issn
1879-0712pii
S0014-2999(11)00914-9journal_volume
670pub_type
杂志文章abstract：:We have assessed the utility of the Cytosensor microphysiometer for studying the pharmacology of recombinant CRF receptors. Chinese hamster ovary cells stably expressing the human CRF1 or CRF2 receptor were perfused in the Cytosensor with bicarbonate-free Hams F12 (pH 7.4) containing 0.2% bovine serum albumin. The ran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00506-3
更新日期：1999-08-27 00:00:00
abstract：:Vagal motor outflow from the dorsal vagal complex is important in the regulation of intestinal motility. The aim of our study was to test the hypothesis that within the dorsal vagal complex, tonic GABA(A)-receptor mediated neurotransmission modulates intestinal motility. The GABA(A) receptor antagonist, bicuculline (m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00071-5
更新日期：1998-04-10 00:00:00
abstract：:The peptides for-Met-Leu-Tyr-OMe, for-Met-Leu-Glu-OMe, for-Met-Leu-Asp-OMe and for-Met-Leu-Ser-OMe were synthesized to investigate the importance of a hydrophilic side chain of the residue at position 3 on biological activities of human neutrophils. A number of in vitro essays were carried out, including: chemotaxis, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01672-8
更新日期：2003-05-23 00:00:00
abstract：:Dorsal root potentials were recorded from urethane-anaesthetised rats. Bicuculline, a recognised GABA antagonist, reduced the amplitude of the potential to 67% of control. Cismethrin, a synthetic pyrethroid insecticide, enhanced the potential to 142% of control values. The convulsions associated with cismethrin poison...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90304-0
更新日期：1980-08-22 00:00:00
abstract：:The role of prejunctional inhibitory and facilitatory muscarinic receptors was investigated in cats with tracheal hyperresponsiveness to vagal stimulation. Intrathoracic airway caliber (total lung resistance (RL) and dynamic compliance (Cdyn] and the diameter of tracheal ring 4 were measured during vagal stimulation a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90409-w
更新日期：1992-01-21 00:00:00
abstract：:When injected directly into the tail, U50,488H is a potent analgesic in the tailflick assay (ED50 3.1 micrograms). The analgesic activity is lost if the radiant heat is focused 1 cm away from the site of injection. The kappa 1-opioid receptor antagonist nor-binaltorphimine given systemically reverses the local analges...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00520-1
更新日期：1996-08-29 00:00:00
abstract：:Dopamine (DA) is thought to have a neurotransmitter role in the spinal cord of the rat. Intrathecal administration of the DA receptor agonist apomorphine has previously been shown to reduce nocifensive responses. The present experiments investigated the site of action of apomorphine, and the mechanisms by which DA ago...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90001-9
更新日期：1985-11-19 00:00:00
abstract：:Recombinant vaccinia viruses harboring the human dopamine D4 receptor cDNA containing two 48 base pair-repeats (D4.2) or the rat dopamine D2 short (D2s) receptor cDNA were used to infect rat-1 fibroblasts. Heterologous expression of both dopamine receptors was demonstrated in binding assays. The affinity constants of ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90011-x
更新日期：1995-06-23 00:00:00
abstract：:The positive chronotropic effect of angiotensin II was studied on the isolated spontaneously beating cat right atria. Angiotensin II and prostacyclin produced similar positive chronotropic and inotropic effects which were not affected by beta-adrenoceptor and histamine H2-receptor blockers. [Sar1,Ile8] angiotensin II,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90260-6
更新日期：1982-09-24 00:00:00
abstract：:Removal of the epithelium increased the responsiveness of isolated guinea-pig trachea to the contractile effects of endothelin. This phenomenon was observed in the presence of indomethacin (5 microM), captopril (10 microM), bacitracin (20 micrograms/ml) or leupeptin (50 microM), but was inhibited by phosphoramidon (10...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90114-3
更新日期：1989-11-21 00:00:00
abstract：:PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family that consists of PPARα, PPARδ, and PAPRγ. Activation of PPARα by ligands including fatty acids and their derivatives as well as some synthetic compounds regulates tumor progression in various tissues. Activated PPARα inhibits or promotes t...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.09.027
更新日期：2015-10-15 00:00:00
abstract：:The relationship between morphine tolerance and pituitary-adrenocortical activity was examined. In rats made tolerant to morphine by implantation of morphine-containing pellets, there was a significant reduction in plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI), whereas no significant changes in c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90499-v
更新日期：1990-06-21 00:00:00
abstract：:The action of calcitonin gene-related peptide (CGRP) on the vasodepressor response to adenosine was investigated in anesthetized rats. I.v. bolus injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg), isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10-300 microg/kg) ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01566-5
更新日期：1998-03-05 00:00:00
abstract：:5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01-10 micr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.08.012
更新日期：2003-09-12 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：:Rats were given powdered diet containing L-DOPA (together with the peripheral decarboxylase inhibitor carbidopa) for a period of 6 months. The estimated daily intake was in the range 20-30 mg/kg. Initially, at 1 week and 1 month, L-DOPA-fed rats exhibited enhanced spontaneous locomotor activity, but this fell to withi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90626-4
更新日期：1982-04-23 00:00:00
abstract：:Store-operated Ca2+ entry is referred to a capacitative current activated by Ca2+ -stores depletion in various non-excitable cells. Neutrophil-like HL-60 cells responded to N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP) by an early O2- production preceded by a [Ca2+]i rise. Cell stimulation in the absence of ext...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00728-6
更新日期：1998-11-20 00:00:00
abstract：:Voltage-gated potassium (Kv) channels are the largest superfamily of potassium (K) channels. A variety of Kv channels are expressed in the vascular smooth muscle cells (SMC). Studies have shown that gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) cause various changes in the human umbilica...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173281
更新日期：2020-09-05 00:00:00
abstract：:Thirty percent of osteosarcoma patients die within 5 years. New agents that induce apoptosis of osteosarcoma cells might be therapeutically useful. Here, we characterized the apoptotic mechanism induced by capsaicin in G292 osteosarcoma cells. Our results show that capsaicin induces an increase in the cytosolic Ca(2+)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.08.011
更新日期：2013-10-15 00:00:00
abstract：:The effects of clozapine on dopamine neurons projecting to the medial-prefrontal cortex, nuclei accumbens and caudatus were compared. Clozapine (1.25 mg/kg i.v.) maximally stimulated the firing rate and burst activity of dopamine neurons projecting to the medialprefrontal cortex. Much higher doses (5 and 10 mg/kg i.v....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00934-0
更新日期：1999-02-05 00:00:00
abstract：:There is some controversy as to whether 5-HT(2C) receptor agonists are anxiogenic or anxiolytic. The effects of the novel 5-HT(2C) receptor agonist, (S)-2-chloro-5-fluoro-indol-1-yl)-1-methyl ethylamine fumarate (RO 60 0175), in three models of anxiety were therefore tested. RO 60 0175 was found to induce hypolocomoti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00706-2
更新日期：2000-01-10 00:00:00
abstract：:Previous studies showed that whereas the potent 5-HT3 receptor antagonist (S)-[3H]zacopride only labels 5-HT3 receptor binding sites, the (R)-enantiomer, (R)-[3H]zacopride, labels these receptors and another class of high-affinity binding sites, named the R sites, in membranes from the rat cerebral cortex and NG 108-1...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90136-w
更新日期：1993-09-15 00:00:00
abstract：:The effects of a 1,5-benzothiazepine derivative, (+)-cis-3-(acetyloxy)-5-[2-[[2-(3,4-dimethoxyphenyl)ethyl]-methyla mino]ethyl]-2,3-dihydro-2-(4-methyoxyphenyl)-1,5-benzothiazepine-4 (5H)-one (DTZ323), on membrane currents were investigated in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)00119-2
更新日期：1997-05-01 00:00:00
abstract：:Aspirin (acetylsalicylic acid), the oldest synthetic drug, was originally used as an anti-inflammatory medication. Being an irreversible inhibitor of COX (prostaglandin-endoperoxide synthase) enzymes that produce precursors for prostaglandins and thromboxanes, it has gradually found several other applications. Sometim...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2019.172762
更新日期：2020-01-05 00:00:00
abstract：:The aim of this study was to investigate the effects of peritonitis on spontaneous contractions of ileum and jejunum smooth muscles isolated from rats. Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.10.064
更新日期：2008-02-02 00:00:00
abstract：:The new antisecretory drug, telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno-[3,4 - b][1,5]benzodiazepin-10-one), was investigated for its inhibition of functionally intact muscarinic receptors involved in gastric acid secretion in rabbit fundic glands, perfused mouse stomach in vitro, p...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90498-4
更新日期：1985-06-07 00:00:00
abstract：:The kappa-opioid receptor agonist, U50,488H (trans-(+-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), has recently been reported to induce dystonia after s.c. administration of 5-10 mg/kg in guinea pigs. The dystonic movements observed in response to U50,488H resembled those previously repo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90600-m
更新日期：1993-05-19 00:00:00
abstract：:Protamine is the only agent approved to reverse heparin-induced anticoagulation. Due to the significant adverse effects of protamine there is an important need for an alternative agent with an improved safety profile. The pharmacodynamics of PM102, a novel peptide-based heparin antagonist, was evaluated and compared t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.03.016
更新日期：2010-06-10 00:00:00
abstract：:We have described here the changes of the biophysical and pharmacological properties of the sarcolemmal ATP-sensitive K+ channels (KATP) of rat skeletal muscle fibres, occurring from an early postnatal period (5 days) to adulthood (210 days). The age-dependent changes of the mean current of the KATP channel (channel a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00965-x
更新日期：1997-03-05 00:00:00
abstract：:Given the differences in the dopamine neurotransmission between the shell and the core of the nucleus accumbens, as well as the differential involvement of these two domains in oral behaviour of rats, it was decided to determine whether or not dopamine D1 and/or dopamine D2 receptors differentially direct oral behavio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00428-n
更新日期：1995-11-03 00:00:00
