Indirubin-3'-oxime suppresses human cholangiocarcinoma through cell-cycle arrest and apoptosis.


:Cholangiocarcinoma (CCA) is one of the most serious of all cancers and a major public health problem. CCA is an extremely invasive cancer, and the survival rate for CCA patients is only 24 months after diagnosis. Although surgery and chemotherapy can extend the survival rate to 5 years, < 20-40% of CCA patients will survive this long; therefore, it is crucial to discover an effective chemotherapeutic agent for CCA. Indirubin-3'-oxime (I3O), a derivative of indirubin, has been shown to suppress cell proliferation and induce cell-cycle arrest and cell apoptosis in various human cancers. In this study, four human CCA cell lines-NOZ, HuCCT1, OCUG-1, and OZ-were used to evaluate the anticancer properties of I3O. Cell viability, cell-cycle arrest, and apoptosis were assessed using Western blotting, immunofluorescence, and flow cytometry analysis. The data show that I3O treatment can inhibit cell proliferation and induce cell-cycle arrest, and caspase-dependent apoptosis in CCA cells. These findings suggest that I3O could suppress tumor growth by regulating the cell cycle and inducing apoptosis, and is a potential therapeutic agent for treating human CCA.


Eur J Pharmacol


Lee MY,Li YZ,Huang KJ,Huang HC,Lin CY,Lee YR




Has Abstract


2018-11-15 00:00:00












  • Turning behaviour following nigral injections of dopamine agonists and glycine.

    abstract::Glycine, ADTN and ergometrine, but not LSD, induced strong dose-related contraversive turning following unilateral microinjections into the substantia nigra (zona reticulata) of conscious rats. The responses to glycine and ADTN were blocked by low doses of systemically injected cis-Z-flupenthixol but were unaffected b...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Andrews CD,Woodruff GN

    更新日期:1982-10-22 00:00:00

  • Potentiation by neuropeptide Y of 5HT2A receptor-mediated contraction in porcine coronary artery.

    abstract::Potentiation by neuropeptide Y of serotonin (5-HT)-induced vasoconstriction was investigated in porcine coronary artery. 5-HT caused concentration-dependent contraction through 5-HT2A receptors. Neuropeptide Y (30 nM) significantly increased the 5HT-induced contraction by 16+/-5% in arteries with intact endothelium. R...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Tsurumaki T,Nagai S,Bo X,Toyosato A,Higuchi H

    更新日期:2006-08-21 00:00:00

  • Effects of piclozotan (SUN N4057), a partial serotonin 1A receptor agonist, on motor complications induced by repeated administration of levodopa in parkinsonian rats.

    abstract::Serotonin 1A receptor agonists have attracted much interest recently as potential therapeutic agents for levodopa-induced motor complications, such as dyskinesia and motor fluctuations. The effects of piclozotan (SUN N4057) on a rat model of advanced Parkinson's disease were investigated. Parkinsonian rats, unilateral...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Tani Y,Ogata A,Koyama M,Inoue T

    更新日期:2010-12-15 00:00:00

  • mRNA expression of tachykinins and tachykinin receptors in different human tissues.

    abstract::The tachykinins substance P, neurokinin A and neurokinin B are involved in many pathophysiological processes. A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to analyse the expression of TAC1 and TAC3, the genes that encode substance P/neurokinin A and neurokinin B, respectively, and the gene...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Pinto FM,Almeida TA,Hernandez M,Devillier P,Advenier C,Candenas ML

    更新日期:2004-06-28 00:00:00

  • The choleretic effects of N-acetylglucosaminides, major urinary metabolites of ursodeoxycholic acid, in bile fistula rats.

    abstract::We investigated the effects of three bile acids conjugated with N-acetylglucosamine, ursodeoxycholate N-acetylglucosaminide, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, on bile flow and biliary excretion of various markers in comparison with ursodeoxycholic acid, taurou...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Iwaki T,Hirabayashi N,Miyazawa N,Takeuchi Y,Ishizaki K,Sakakura H,Kasai H,Maeda M,Araki T

    更新日期:1998-12-11 00:00:00

  • Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

    abstract::Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related c...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章,评审


    authors: García-Pardo MP,Roger-Sanchez C,Rodríguez-Arias M,Miñarro J,Aguilar MA

    更新日期:2016-06-15 00:00:00

  • Contractile actions of imidazoline alpha-adrenoceptor agonists and effects of noncompetitive alpha1-adrenoceptor antagonists in human vas deferens.

    abstract::The contractile actions of imidazoline alpha-adrenoceptor agonists were investigated in human vas deferens longitudinal and circular muscle. The effects of phenoxybenzamine were studied in comparison to dibenamine and SZL-49 (4-amino-6,7-dimethoxy-2-quinazolinyl-4-(2-bicyclo[2,2,2]octa-2,5-dienylcarbonyl-2-piperazine)...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Amobi N,Guillebaud J,Kaisary A,Lloyd-Davies RW,Turner E,Smith IC

    更新日期:2003-02-21 00:00:00

  • Mitochondrial outer membrane voltage-dependent anion channel is involved in renal dysfunction in a spontaneously hypertensive rat carrying transfer RNA mutations.

    abstract::Mitochondrial DNA mutations promote hypertensive renal dysfunction, but the molecular mechanism remains unclear. This study compared renal damage between spontaneously hypertensive rats (SHR) and SHR with mitochondrial transfer (t)RNA mutations. To investigate the role of mitochondrial outer membrane voltage-dependent...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Zhu C,Tian L,Yang H,Chen P,Li Y,Liu Y

    更新日期:2019-12-15 00:00:00

  • Regional distribution of mRNA for a putative kainate receptor in rat brain.

    abstract::A cDNA clone which encodes a putative kainate receptor was prepared with the polymerase chain reaction; from this, 'antisense' RNA fragments were produced and used to evaluate the distribution of mRNA for the kainate-receptor in rat brain with in situ hybridization techniques. The data demonstrate marked regional diff...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Gall C,Sumikawa K,Lynch G

    更新日期:1990-09-18 00:00:00

  • Effect of N,N-dimethyl-p-methoxyphenylethylamine on blood pressure and brain catecholamines in DOCA-saline hypertensive rats.

    abstract::Intraperitoneal and intraventricular injections of N,N-dimethyl-p-methoxyphenyl ethylamine (PMPEA) decreased blood pressure in conscious DOCA-saline hypertensive rats. Bilateral injection of this agent into the nucleus tractus solitarii (NTS) of anaesthetized normotensive rats also caused a decrease in blood pressure....

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Shalita B,Versteeg DH,De Jong W

    更新日期:1982-11-19 00:00:00

  • Enkephalin release and opioid receptor activation does not mediate the antinociceptive or sedative/hypnotic effects of nitrous oxide.

    abstract::In previous studies using Fos expression as a marker of neuronal activation, we showed that nitrous oxide (N(2)O) activates bulbospinal noradrenergic neurons in rats and that destruction of these neuronal pathways leads to loss of N(2)O antinociceptive action. Based on previous rat studies it has been proposed that th...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Kingery WS,Sawamura S,Agashe GS,Davies MF,Clark JD,Zimmer A

    更新日期:2001-09-07 00:00:00

  • In vitro studies with ICI 169,369, a chemically novel 5-HT antagonist.

    abstract::ICI 169,369 is a chemically novel 5-HT antagonist that has higher affinity for the 5-HT2 binding sites in rat cortex than it has for 5-HT1 sites (Ki 1.79 x 10(-8) and 1.58 x 10(-6) M, respectively). In isolated tissue preparations ICI 169,369 was shown to be a competitive antagonist of 5-HT on the rabbit aorta, pig co...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Blackburn TP,Thornber CW,Pearce RJ,Cox B

    更新日期:1988-06-10 00:00:00

  • Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors.

    abstract::The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 rec...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Malinowska B,Göthert M,Godlewski G,Wróbel B,Bönisch H,Buczko W

    更新日期:1995-05-26 00:00:00

  • Role of CGRP and GABA in the hypotensive effect of intrathecally administered anandamide to anesthetized rats.

    abstract::In urethane-anesthetized rats the intrathecal (i.t.) injection of 100 nmol anandamide produced a hypotensive effect (-19.3+/-1.6 mm Hg; n=6) that was mimicked by i.t. administration of 0.25 nmol calcitonin gene-related peptide (CGRP; -26.2+/-1.8 mm Hg, n=4). Both effects were antagonized either by the CGRP receptor an...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: García Mdel C,Adler-Graschinsky E,Celuch SM

    更新日期:2006-02-17 00:00:00

  • Impaired hypotensive responses induced by intrathecally injected drugs in fructose-fed rats.

    abstract::Blood pressure responses to intrathecal (i.t.) injection of neurochemicals were examined in the fructose-fed rat, an experimental model of metabolic syndrome.Sprague-Dawley rats receiving either tap water or water containing 10% fructose during 8 weeks were anesthetized with sodium pentobarbital. The endocannabinoid a...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: García Mdel C,Godoy YC,Celuch SM

    更新日期:2013-04-15 00:00:00

  • The thromboxane A2/prostaglandin endoperoxide receptor antagonist activity of CV-4151, a thromboxane A2 synthetase inhibitor.

    abstract::The thromboxane A2/prostaglandin endoperoxide (TXA2/PGH2) receptor antagonist activity of CV-4151, a potent TXA2 synthetase inhibitor, was examined. CV-4151 inhibited guinea pig and human platelet aggregation induced by U-44069 with IC50 values of 1.2 +/- 0.3 X 10(-5) and 1.9 +/- 0.4 X 10(-5) M, respectively, and inhi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Imura Y,Terashita Z,Shibouta Y,Nishikawa K

    更新日期:1988-03-15 00:00:00

  • Vasopressin V(1) receptor-mediated activation of central sympatho-adrenomedullary outflow in rats.

    abstract::The present study was designed to characterize the vasopressin receptor subtype involved in the vasopressin-induced activation of the central sympatho-adrenomedullary outflow using urethane-anesthetized rats. Intracerebroventricularly (i.c.v.) administered vasopressin (0.1, 0.2 and 0.5 nmol/animal) dose-dependently el...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Okada S,Murakami Y,Nakamura K,Yokotani K

    更新日期:2002-12-13 00:00:00

  • Pharmacological studies with several analogs of mazindol: correlation between effects on dopamine uptake and various in vivo responses.

    abstract::Several structural analogs of mazindol were tested as inhibitors of the uptake of [3H] dopamine in rat neostriatum, of [3H] norepinephrine in rat occipital cortex and of [3H] serotonin in whole rat brain. A rather wide range of potencies was observed but a number of the drugs were even more potent than mazindol as upt...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Heikkila RE,Babington RG,Houlihan WJ

    更新日期:1981-05-08 00:00:00

  • Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta.

    abstract::The present work describes the mechanisms involved in the vasorelaxant effect of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Kaurenoic acid (10, 50 and 100 microM) concentration-dependently inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or -denuded rat aortic rings. Kau...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Tirapelli CR,Ambrosio SR,da Costa FB,Coutinho ST,de Oliveira DC,de Oliveira AM

    更新日期:2004-05-25 00:00:00

  • Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats.

    abstract::Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Salomé N,Haage D,Perrissoud D,Moulin A,Demange L,Egecioglu E,Fehrentz JA,Martinez J,Dickson SL

    更新日期:2009-06-10 00:00:00

  • Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro.

    abstract::The action of antidepressants on cell proliferation (bromodeoxyuridine (BrdU) or [3H]thymidine incorporation) was studied in the adult rat hippocampus in vivo and in neural precursors (immature rat cerebellar granule cells) in vitro. In vivo, prolonged (21 days) but not acute (single) intraperitoneal treatment with fl...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Manev H,Uz T,Smalheiser NR,Manev R

    更新日期:2001-01-05 00:00:00

  • Tetrahydrobiopterin analogues with NO-dependent pulmonary vasodilator properties.

    abstract::Reduced NO levels due to the deficiency of tetrahydrobiopterin (BH(4)) contribute to impaired vasodilation in pulmonary hypertension. Due to the chemically unstable nature of BH(4), it was hypothesised that oxidatively stable analogues of BH(4) would be able to support NO synthesis to improve endothelial dysfunction i...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Kunuthur SP,Milliken PH,Gibson CL,Suckling CJ,Wadsworth RM

    更新日期:2011-01-10 00:00:00

  • Vasopressin-induced contraction in the rat basilar artery in vitro.

    abstract::Vasopressin ([Arg(8)]vasopressin)-induced contraction was characterized using receptor agonists and antagonists for vasopressin and channel blockers in the rat basilar artery ring preparations. Vasopressin induced rhythmic contractions superimposed on a contraction in endothelium-intact preparations but not in denuded...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Katori E,Ohta T,Nakazato Y,Ito S

    更新日期:2001-03-23 00:00:00

  • Vasoconstricting effect in rat aorta caused by thaliporphine isolated from the plant Neolitsea konishii K.

    abstract::Thaliporphine (0.1-100 microM) produced sustained, concentration-dependent contraction in isolated rings of rat aorta. Thaliporphine (ED50 = 1.5 +/- 0.5 microM) was less potent than endothelin (ED50 = 3.9 +/- 0.4 nM), but was more potent than Bay K 8644 (ED50 = 5.5 +/- 0.6 microM). Thaliporphine also contracted guinea...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Teng CM,Yu SM,Lee SS,Ko FN,Su MJ,Huang TF

    更新日期:1993-03-16 00:00:00

  • Changes in the serotonin and 5-hydroxyindoleacetic acid contents in rat brain after ethanol and disulfiram treatments.

    abstract::Disulfiram (700 mg/kg, p.o.) significantly increased the brain levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rats. Ethanol (1 g/kg and 2 x 1.5 g/kg, i.p.) did not affect the 5-HT level, but at the higher dose it significantly increased the 5-HIAA level. When disulfiram was given in combination ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Fukumori R,Minegishi A,Satoh T,Kitagawa H,Yanaura S

    更新日期:1980-01-25 00:00:00

  • Involvement of serotonin receptors 5-HT1 and 5-HT2 in 12(S)-HPETE-induced scratching in mice.

    abstract::The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)-HPETE)-induced scratching were studied in ICR mice. In a recent paper, we demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302 (BLT(1) receptor antagonist), but by LY255283 (BLT(2) receptor antagonist). In the pres...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Kim DK,Kim HJ,Kim H,Koh JY,Kim KM,Noh MS,Kim JJ,Lee CH

    更新日期:2008-01-28 00:00:00

  • The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig.

    abstract::The concentration dependences of the Ca(2+)-sensitizing and the phosphodiesterase-inhibitory effects of levosimendan (the (-) enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile) and its active metabolite, OR-1896 (the (-) enantiomer of N-[4-(1,4,5,6-tetrahydro-4-methyl...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Szilágyi S,Pollesello P,Levijoki J,Kaheinen P,Haikala H,Edes I,Papp Z

    更新日期:2004-02-13 00:00:00

  • Effect of local bleomycin sulfate application on seroma formation in a rat mastectomy and axillary lymph node dissection model.

    abstract::Seroma formation is one of the most common complications following breast cancer surgery. It may lead to delay of adjuvant therapies and increasement of therapy costs. Bleomycin sulfate is a sclerosing antibiotic with antineoplastic efficacy. It is locally used in the treatment of pleural effusion. The present study a...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Eser M,Gökçeimam M,Eyvaz K,Tutal F,Geçer MÖ,Göktaş S,Uzun H,Kaptanoglu L,Kurt N

    更新日期:2014-01-15 00:00:00

  • The spasmogenic effect of caffeine in trachealis isolated from control and actively sensitized guinea-pigs.

    abstract::The spasmogenic activity of caffeine (10 mM) was evaluated in tracheal strips obtained from control and sensitized guinea-pigs then pretreated with indomethacin (2.8 microM) and cooled to 20 degrees C. The contraction elicited by caffeine was inhibited by verapamil (100 microM), trifluoperazine (100 and 500 microM) an...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Ortiz JL,Cortijo J,Morcillo EJ,Sanz C,Perpiñá M,Esplugues J

    更新日期:1988-12-13 00:00:00

  • Effect of vitamin K2 (menatetrenone) on osteoclast-like cell formation in mouse bone marrow cultures.

    abstract::The effects of menatetrenone, a vitamin K2 homologue, on osteoclast-like cell formation in mouse bone marrow culture were investigated. After 7 days of incubation, menatetrenone at 10(-6) M, 3 x 10(-6) M and 10(-5) M dose dependently inhibited the tartrate-resistant acid phosphatase-positive multinucleated cell format...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Akiyama Y,Hara K,Tajima T,Murota S,Morita I

    更新日期:1994-09-22 00:00:00