Suppression of beta-catenin signaling by liver X receptor ligands.


:The nuclear receptors liver X receptor (LXR) alpha and LXRbeta serve as oxysterol receptors and play an important role in the regulation of lipid metabolism. We investigated the potential effects of LXRs on pathways of colon carcinogenesis and found that LXR activation suppresses the transactivation activity of beta-catenin, a key molecule in Wnt signaling. LXRalpha and LXRbeta inhibited beta-catenin transactivation of T cell factor-mediated transcription in a ligand-dependent manner. LXR activation suppressed an oncogenic beta-catenin, which has phosphorylation site mutations, and did not change beta-catenin protein expression in cells. In contrast, beta-catenin enhanced LXR transactivation activity. Nuclear LXRs and beta-catenin were coimmunoprecipitated in colon cancer HCT116 cells, and in vitro experiments showed that LXRs bind directly to the Armadillo repeat region of beta-catenin in a ligand-independent manner. LXR ligand decreased mRNA expression of beta-catenin targets, MYC, MMP7 and BMP4, and recruited LXRs to MYC and MMP7 promoters. Transfection of a dominant negative LXR to HCT116 cells and experiments using LXR-null cells showed the involvement of cellular LXRs in beta-catenin suppression and proliferation inhibition. The results show lipid-sensing receptor LXRs regulate the beta-catenin activity and cellular proliferation.


Biochem Pharmacol


Biochemical pharmacology


Uno S,Endo K,Jeong Y,Kawana K,Miyachi H,Hashimoto Y,Makishima M




Has Abstract


2009-01-15 00:00:00














  • Polymerization of the triphosphates of AraC, 2',2'-difluorodeoxycytidine (dFdC) and OSI-7836 (T-araC) by human DNA polymerase alpha and DNA primase.

    abstract::OSI-7836 (4'-thio-araC, T-araC) is a nucleoside analogue that shows efficacy against solid tumor xenograft models. We examined how the triphosphates of OSI-7836 (T-araCTP), cytarabine (araCTP), and gemcitabine (dFdCTP) affected the initiation of new DNA strands by the pol alpha primase complex. Whereas dFdCTP very wea...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Richardson KA,Vega TP,Richardson FC,Moore CL,Rohloff JC,Tomkinson B,Bendele RA,Kuchta RD

    更新日期:2004-12-15 00:00:00

  • Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

    abstract::Human ABCG2 is a plasma membrane glycoprotein that provides physiological protection against xenobiotics. ABCG2 also significantly influences biodistribution of drugs through pharmacological tissue barriers and confers multidrug resistance to cancer cells. Moreover, ABCG2 is the molecular determinant of the side popul...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hegedüs C,Truta-Feles K,Antalffy G,Várady G,Német K,Ozvegy-Laczka C,Kéri G,Orfi L,Szakács G,Settleman J,Váradi A,Sarkadi B

    更新日期:2012-08-01 00:00:00

  • DNA-DNA interstrand crosslinking by dimethyanesulphonic acid esters. Correlation with cytotoxicity and antitumour activity in the Yoshida lymphosarcoma model and relationship to chain length.

    abstract::Members of the homologous series of nine antitumour dimethanesulphonic acid esters, with the exception of ethylene dimethanesulphonate (EDMS), were found to cause DNA-DNA interstrand crosslinking in cells derived from the transplantable rodent Yoshida lymphosarcoma. The ability of the series to induce interstrand cros...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bedford P,Fox BW

    更新日期:1983-08-01 00:00:00

  • The possible involvement of the phospholipid phase of membranes in mediating the effects of verapamil on Ca2+ transport.

    abstract::The effect of verapamil in a model system of A23187-induced Ca2+-uptake into liposomes was studied. This was done in order to separate the effects of verapamil on the lipid phase of membranes from its effects on membraneous proteins. In the absence of A23187, the liposomes exhibited a very low Ca2+ permeability, which...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Erdreich A,Rahamimoff H

    更新日期:1987-06-01 00:00:00

  • The multikinase inhibitor axitinib is a potent inhibitor of human CYP1A2.

    abstract::The tyrosine kinase inhibitors (TKIs) and multikinase inhibitors (MKIs) are oncology drugs of increasing importance that have improved the treatment of multiple tumors types. In some patients these agents produce adverse effects, including pharmacokinetic drug-drug interactions, due to cytochrome P450 (CYP) inhibition...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gu R,Hibbs DE,Ong JA,Edwards RJ,Murray M

    更新日期:2014-03-15 00:00:00

  • Investigation of the cellular mechanism of inhibition of formyl-methionyl-leucyl-phenylalanine-induced superoxide anion generation in rat neutrophils by 2-benzyloxybenzaldehyde.

    abstract::The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in rat neutrophils, and the underlying mechanism of this inhibition was assessed. CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4....

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang JP,Chang LC,Lin YL,Hsu MF,Chang CY,Huang LJ,Kuo SC

    更新日期:2003-04-01 00:00:00

  • Biological activity and molecular interaction of a netropsin-acridine hybrid ligand with chromatin and topoisomerase II.

    abstract::A hybrid molecule, which combines an anilinoacridine chromophore related to the antitumour drug amsacrine (m-AMSA) and a bispyrrole moiety analogous to the antiviral agent netropsin, has been examined for its ability to bind chromatin and to modulate the activity of topoisomerase II. The results show that the presence...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bailly C,Collyn-d'Hooghe M,Lantoine D,Fournier C,Hecquet B,Fosse P,Saucier JM,Colson P,Houssier C,Hénichart JP

    更新日期:1992-02-04 00:00:00

  • Regulatory effects of zinc and copper on the calcium transport system in rat liver nuclei. Relation to SH groups in the releasing mechanism.

    abstract::In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the ef...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yamaguchi M

    更新日期:1993-02-24 00:00:00

  • Thiocolchicine dimers: a novel class of topoisomerase-I inhibitors.

    abstract::During a cellular screening of thiocolchicine analogs, thiocolchicine dimers resulted particularly active in cisplatin-resistant A2780-CIS cells. In order to discover by which mechanism(s) thiocolchicine dimers overcame cisplatin resistance, p53, p21waf1 and MLH1 were assessed by Western blot. Results pointed out that...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Raspaglio G,Ferlini C,Mozzetti S,Prislei S,Gallo D,Das N,Scambia G

    更新日期:2005-01-01 00:00:00

  • Inhibition of purine catabolism by benzbromarone in isolated rat liver cells. Comparison with allopurinol and probenecid.

    abstract::Benzbromarone, a potent uricosuric agent, inhibited allantoin production in isolated hepatocytes at concentrations half to ten times greater than therapeutic plasma levels of the drug. In addition, the drug at these concentrations also markedly inhibited xanthine oxidase (EC, an enzyme involved in the regula...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rodilla F,Sanchez-Beltran MJ,Izquierdo R,Gomez-Ruiz MD,Cabo J

    更新日期:1988-10-01 00:00:00

  • UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.

    abstract::Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Juncker T,Cerella C,Teiten MH,Morceau F,Schumacher M,Ghelfi J,Gaascht F,Schnekenburger M,Henry E,Dicato M,Diederich M

    更新日期:2011-01-01 00:00:00

  • Catecholamines and the kinetics of lipolysis in isolated rat adipocytes. Statistical analysis and handling of day-to-day variability in dose-response curves: a general procedure for assessing and manipulating dose-response data.

    abstract::(1) As a first step in studying the kinetics of the lipolytic system of rat adipocytes, the day-to-day variation between dose-response curves has been analysed. (2) Methods are described for the evaluation of large quantities of data relating noradrenaline to lipolysis. (3) A 'clustering' technique is presented which ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Davies JI,Cooper DM,Everett D

    更新日期:1982-03-01 00:00:00

  • Therapeutic implications of the prostaglandin pathway in Alzheimer's disease.

    abstract::An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Cudaback E,Jorstad NL,Yang Y,Montine TJ,Keene CD

    更新日期:2014-04-15 00:00:00

  • Role of ethanol metabolism in the alcohol-induced increase in urinary folate excretion in rats.

    abstract::Chronic ethanol use can lead to folic acid deficiency in humans. In rats, acute doses of ethanol produce a marked increase in the urinary excretion of folate which is followed by a decrease in plasma folate levels. To assess the respective roles of ethanol and its metabolism in these effects, five groups of male Sprag...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McMartin KE,Collins TD

    更新日期:1983-09-01 00:00:00

  • Pharmacodynamic approach to study the gene transfer process employing non-viral vectors.

    abstract::In the present work we set out to apply pharmacodynamic concepts derived from dose-response curves (Potency and Efficacy) to characterize the gene transfer efficiency of a vector:DNA complex. We employed two widely used vectors, the cationic lipid DOTAP (N,N, N-trimethyl 1-2-3-bis (1-oxo-9-octa-decenyl)oxy-(Z, Z)-1-pr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Aliño SF,Escrig E,Revert F,Guillem VM,Crespo A

    更新日期:2000-12-15 00:00:00

  • Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response.

    abstract::Nuclear factor-E2-related factor 2 (Nrf2) is a master transcription factor in antioxidant response, protecting against oxidative damage and various diseases. Previous studies suggest that Nrf2 is suppressed in fibrotic skin and Nrf2 agonists represent a therapeutic strategy, which is mainly attributed to Nrf2 function...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wu R,Zhang H,Zhao M,Li J,Hu Y,Fu J,Pi J,Wang H,Xu Y

    更新日期:2020-04-01 00:00:00

  • Heme and hemoproteins in streptozotocin-diabetic female rats.

    abstract::Alterations in heme biosynthetic and degradative capabilities and in the activities of several heme-containing enzymes were examined in hepatic tissues of streptozotocin (STZ)-diabetic female Sprague-Dawley rats. Activities were measured 10, 30 and 90 days following the administration of STZ (65 mg/kg, i.v.). The acti...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bitar M,Weiner M

    更新日期:1983-06-15 00:00:00

  • Drug metabolism in hepatocyte sandwich cultures of rats and humans.

    abstract::Adult hepatocytes from rat and man were maintained for 2 weeks between two gel layers in a sandwich configuration to study the influence of this culture technique on the preservation of basal activities of xenobiotic-metabolizing phase I and phase II enzymes. The response of these enzyme activities to an enzyme induce...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kern A,Bader A,Pichlmayr R,Sewing KF

    更新日期:1997-10-01 00:00:00

  • Increased glutathione peroxidase activity in human blood mononuclear cells upon in vitro incubation with n-3 fatty acids.

    abstract::Fish oil-enriched diets have been shown to increase the n-3 polyunsaturated fatty acid (PUFA) content of cell membranes, in vivo, and to simultaneously enhance the glutathione peroxidase (glutathione: H2O2 oxidoreductase, EC (GSH-Px) activity of platelets and erythrocytes both in animals and humans. The pres...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Joulain C,Prigent AF,Némoz G,Lagarde M

    更新日期:1994-04-20 00:00:00

  • The two faces of aldehyde oxidase: Oxidative and reductive transformations of 5-nitroquinoline.

    abstract::Aldehyde oxidase (AOX) is a cytosolic enzyme responsible for the metabolism of some drugs and drug candidates. AOX catalyzes the oxidative hydroxylation of substrates including several aliphatic and aromatic aldehydes, and nitrogen-containing heterocyclic compounds. AOX is also reported to catalyze the reductive metab...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Paragas EM,Humphreys SC,Min J,Joswig-Jones CA,Jones JP

    更新日期:2017-12-01 00:00:00

  • Differential patterns of inhibition of the sugar transporters GLUT2, GLUT5 and GLUT7 by flavonoids.

    abstract::Only limited data are available on the inhibition of the sugar transporter GLUT5 by flavonoids or other classes of bioactives. Intestinal GLUT7 is poorly characterised and no information exists concerning its inhibition. We aimed to study the expression of GLUT7 in Caco-2/TC7 intestinal cells, and evaluate inhibition ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Gauer JS,Tumova S,Lippiat JD,Kerimi A,Williamson G

    更新日期:2018-06-01 00:00:00

  • Immunosuppressive and anti-inflammatory properties of a major protein secreted from the epithelium of the rat seminal vesicles.

    abstract::The nonspecies specific immunosuppressive and anti-inflammatory properties of a major protein (SV-IV) secreted from the epithelium of rat seminal vesicles (SV) are described. To detect the immunosuppressive effect, peripheral blood lymphocytes (PBL) were pretreated for 2 hr at 37 degrees with SV-IV, and the protein wa...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Metafora S,Peluso G,Persico P,Ravagnan G,Esposito C,Porta R

    更新日期:1989-01-01 00:00:00

  • Isolation, synthesis and characterization of ω-TRTX-Cc1a, a novel tarantula venom peptide that selectively targets L-type Cav channels.

    abstract::Spider venoms are replete with peptidic ion channel modulators, often with novel subtype selectivity, making them a rich source of pharmacological tools and drug leads. In a search for subtype-selective blockers of voltage-gated calcium (CaV) channels, we isolated and characterized a novel 39-residue peptide, ω-TRTX-C...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Klint JK,Berecki G,Durek T,Mobli M,Knapp O,King GF,Adams DJ,Alewood PF,Rash LD

    更新日期:2014-05-15 00:00:00

  • Induction of G(2)/M phase arrest and apoptosis by a new synthetic anti-cancer agent, DW2282, in promyelocytic leukemia (HL-60) cells.

    abstract::We studied the effect of DW2282-,[(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indoline-5-sulfonyl-4,5-dihydro-2-imidazolone].hydrochloride], a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. DW2282, a diarylsulfonylu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Piao W,Yoo J,Lee DK,Hwang HJ,Kim JH

    更新日期:2001-12-01 00:00:00

  • Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via α7 nAChR-dependent and -independent mechanisms.

    abstract::Glutamatergic hypofunction and elevated levels of kynurenic acid (KYNA) in the brain are common features of patients with schizophrenia. In vivo studies indicate that in the hippocampus KYNA decreases glutamate levels, presumably via inhibition of α7 nicotinic receptors (nAChRs). Here we tested the hypothesis that bas...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Banerjee J,Alkondon M,Albuquerque EX

    更新日期:2012-10-15 00:00:00

  • Inversely-correlated inhibition of human 5-lipoxygenase activity by BAY X1005 and other quinoline derivatives in intact cells and a cell-free system--implications for the function of 5-lipoxygenase activating protein.

    abstract::A series of quinoline derivatives were analysed for the influence on leukotriene synthesis as a parameter for 5-LOX (EC activity in a cell-free system of the 10,000 g supernatant of human PMNL (polymorphonuclear leukocytes). The ratios of the IC50 values for leukotriene synthesis inhibition in this cell-fr...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Hatzelmann A,Goossens J,Fruchtmann R,Mohrs KH,Raddatz S,Müller-Peddinghaus R

    更新日期:1994-06-15 00:00:00

  • Site-directed mutagenesis at the human B2 receptor and molecular modelling to define the pharmacophore of non-peptide bradykinin receptor antagonists.

    abstract::Combining site-directed mutagenesis with information obtained from molecular modelling of the bradykinin (BK) human B2 receptor (hB2R) as derived from the bovine rhodopsin crystal structure [Science 289 (2000) 739], we previously defined a putative binding mode for the non-peptide B2 receptor antagonists, FR173657 and...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Meini S,Cucchi P,Bellucci F,Catalani C,Faiella A,Rotondaro L,Quartara L,Giolitti A,Maggi CA

    更新日期:2004-02-15 00:00:00

  • Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction.

    abstract::Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to antic...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Poerschke RL,Moos PJ

    更新日期:2011-01-15 00:00:00

  • Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine.

    abstract::L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Georges B,Galland S,Rigault C,Le Borgne F,Demarquoy J

    更新日期:2003-05-01 00:00:00

  • Role of mechanical and redox stress in activation of mitogen-activated protein kinases in primary cultured rat hepatocytes.

    abstract::Mechanical stress is known to activate signaling cascades, including mitogen-activated protein kinase (MAPK) pathways. Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanica...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kim SK,Woodcroft KJ,Oh SJ,Abdelmegeed MA,Novak RF

    更新日期:2005-12-05 00:00:00