Human ATP-Binding Cassette transporters ABCB1 and ABCG2 confer resistance to CUDC-101, a multi-acting inhibitor of histone deacetylase, epidermal growth factor receptor and human epidermal growth factor receptor 2.

Abstract:

:CUDC-101 is the first small-molecule inhibitor designed to simultaneously inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and histone deacetylase (HDAC) in cancer cells. Recently, in its first in human phase I study, CUDC-101 showed promising single agent activity against advanced solid tumors and favorable pharmacodynamic profile. However, the risk of developing drug resistance to CUDC-101 can still present a significant therapeutic challenge to clinicians in the future. One of the most common mechanisms of developing multidrug resistance (MDR) in cancer is associated with the overexpression of ATP-binding cassette (ABC) drug transporters ABCB1 and ABCG2. Together, they are able to reduce the efficacy and modify the pharmacological properties of anti-cancer agents, including many small molecule tyrosine kinase inhibitors (TKIs). Here, we have investigated the impact of ABCB1 and ABCG2 on the efficacy of CUDC-101 in human cancer cells. We revealed that although CUDC-101 has potent antiproliferative and proapoptotic activities against most cancer cell lines, the overexpression of ABCB1 or ABCG2 in cancer cells significantly reduced the activity of CUDC-101 against HDAC, EGFR and HER2, as well as its cytotoxicity and proapoptotic activity. Moreover, we showed that CUDC-101 modulated the function of both transporters without affecting the protein expression of either ABCB1 or ABCG2. More importantly, our study provides support for the rationale of combining CUDC-101 with modulators of ABC drug transporters to improve drug efficacy and overcome multidrug resistance associated with the overexpression of ABCB1 and ABCG2.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Wu CP,Hsiao SH,Su CY,Luo SY,Li YQ,Huang YH,Hsieh CH,Huang CW

doi

10.1016/j.bcp.2014.10.003

subject

Has Abstract

pub_date

2014-12-15 00:00:00

pages

567-76

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(14)00588-7

journal_volume

92

pub_type

杂志文章
  • 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

    doi:10.1016/j.bcp.2010.08.025

    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

  • Reversal of antigen-dependent signaling by two mutations in antibody/receptor chimera: implication of inverse agonism in cytokine receptor superfamily.

    abstract::Understanding the receptor activation mechanism is essential for the rational design of pharmacologically active ligand molecules. However, the activation mechanism of most cytokine receptors remains still unclear, and while agonism and antagonism have been described for ligand-mimetic peptides, there has been no repo...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2004.04.014

    authors: Kawahara M,Ishii S,Tsumoto K,Kumagai I,Ueda H,Nagamune T

    更新日期:2004-08-01 00:00:00

  • Dissociation of covalent binding from the oxidative effects of acetaminophen. Studies using dimethylated acetaminophen derivatives.

    abstract::The cytotoxic effects of 10 mM acetaminophen (APAP) in primary cultures of non-induced mouse hepatocytes are accompanied by depletion of intracellular glutathione (GSH), arylation of protein, and loss of protein sulfhydryl (PSH) groups. Investigation of the stoichiometry of the covalent binding and PSH loss after APAP...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(88)90686-7

    authors: Birge RB,Bartolone JB,Nishanian EV,Bruno MK,Mangold JB,Cohen SD,Khairallah EA

    更新日期:1988-09-15 00:00:00

  • Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells.

    abstract::We have reported that in renal epithelial A6 cells flavones stimulate the transepithelial Cl- secretion by activating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel and/or the Na+/K+/2Cl- cotransporter. On the other hand, it has been established that cAMP activates the CFTR Cl- channel and ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2003.10.026

    authors: Niisato N,Nishino H,Nishio K,Marunaka Y

    更新日期:2004-02-15 00:00:00

  • Potentiated hepatotoxicity from concurrent administration of acetaminophen and allyl alcohol to rats.

    abstract::Female Wistar rats were treated with acetaminophen 3.0 g/kg BW and allyl alcohol 75 microliter/kg BW by gastric tube. Hepatic function, measured as galactose elimination capacity and prothrombin index, was reduced to about 0.40 times control value. Plasma alanine transferase activity was elevated more and earlier afte...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(85)90750-6

    authors: Poulsen HE,Lerche A,Pedersen NT

    更新日期:1985-03-15 00:00:00

  • Determination of the magnitude and enantioselectivity of ligand binding to rat and rabbit serum albumins using immobilized-protein high performance liquid chromatography stationary phases.

    abstract::Rat, rabbit and human serum albumins were immobilized on an HPLC stationary phase, and the resulting phases were tested for their abilities to determine the extent and enantioselectivity of ligand binding to the respective albumins. A series of achiral and chiral compounds were chromatographed on the phases including ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90478-f

    authors: Massolini G,Aubry AF,McGann A,Wainer IW

    更新日期:1993-10-05 00:00:00

  • Characterization of the purine-reactive site of the rat testis cytosolic adenylate cyclase.

    abstract::Naturally soluble rat germ cell adenylate cyclase was inhibited by adenosine and the adenosine analogs, 9-beta-D-arabinofuranosyl adenine (AFA) and 2',5'-dideoxyadenosine (DDA), all of which inhibited hormone-sensitive adenylate cyclases at the "P" site. The IC50 values for adenosine and DDA were approximately 0.1 and...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(87)90487-4

    authors: Onoda JM,Braun T,Wrenn SM Jr

    更新日期:1987-06-15 00:00:00

  • Proteasomal inhibition potentiates drugs targeting DNA topoisomerase II.

    abstract::The reaction mechanism of DNA topoisomerase II (TOP2) involves a covalent double-strand break intermediate in which the enzyme is coupled to DNA via a 5'-phosphotyrosyl bond. This normally transient enzyme-bridged break is stabilised by drugs such as mitoxantrone, mAMSA, etoposide, doxorubicin, epirubicin and idarubic...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2015.12.015

    authors: Lee KC,Bramley RL,Cowell IG,Jackson GH,Austin CA

    更新日期:2016-03-01 00:00:00

  • Celecoxib transiently inhibits cellular protein synthesis.

    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...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2007.08.029

    authors: Pyrko P,Kardosh A,Schönthal AH

    更新日期:2008-01-15 00:00:00

  • Effect of sodium orthovanadate on the hepatobiliary clearance of rose bengal in streptozotocin-induced diabetic rats.

    abstract::Sodium orthovanadate is known to promote glucose uptake in muscle and adipose tissues and has been suggested as a possible oral hypoglycemic agent. In addition, insulin-dependent diabetes has been shown to alter the hepatobiliary clearance of several drugs in rats. This study has determined whether orthovanadate, like...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90617-6

    authors: Watkins JB 3rd,Bauman ME,Beaty TM

    更新日期:1993-12-14 00:00:00

  • Inhibition of nucleotide excision repair and sensitisation of cells to DNA cross-linking anticancer drugs by F 11782, a novel fluorinated epipodophylloid.

    abstract::F 11782, or 2',3'-bis-pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D-glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2-N-methyl glucamine salt, a novel dual catalytic inhibitor of topoisomerases I and II, was identified as a potent inhibitor of nucleotide excision repair (NER) by screening procedures using t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00835-8

    authors: Barret JM,Cadou M,Hill BT

    更新日期:2002-01-15 00:00:00

  • Dual effect of ebselen on mitochondrial permeability transition.

    abstract::This study reports an investigation on the effect of the seleno-organic compound ebselen on rat liver mitochondria. We show that low concentrations of ebselen induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling and loss of membrane potential. These effects were mediated by the o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(03)00114-x

    authors: Morin D,Zini R,Ligeret H,Neckameyer W,Labidalle S,Tillement JP

    更新日期:2003-05-15 00:00:00

  • Measurement of blood levels of neuroleptics and metabolites by combined high performance liquid chromatography-radioreceptor assay for D2 and sigma sites.

    abstract::The dopamine (D2) receptor blocking property of antipsychotic medications has been proposed as the mechanism of the therapeutic activity of this class of drugs. This property has also been exploited as a method to quantify therapeutic levels of these drugs in patients. However, the lack of correlation among dosage, bl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90238-4

    authors: Hoffman DW,Shillcutt SD,Edkins RD

    更新日期:1989-03-01 00:00:00

  • In vivo iron mobilisation evaluation of hydroxypyridinones in 59Fe-ferritin-loaded rat model.

    abstract::Although there are a number of well-characterised animal models available for testing and comparing the efficacy of iron chelators, most are expensive to operate and are not capable of providing rapid and reproducible results. The method described herein is based on the labelling of rat liver with 59Fe using rat 59Fe-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(98)00319-0

    authors: Liu ZD,Lu SL,Hider RC

    更新日期:1999-03-01 00:00:00

  • Bismuth ions inhibit the biological activity of non-amidated gastrins in vivo.

    abstract::The peptide hormone gastrin binds two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. Bi3+ ions also bind to glycine-extended gastrin17 (Ggly), but inhibit Ggly-induced cell proliferation and migration in gastrointestinal cell lin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2011.11.030

    authors: Kovac S,Loh SW,Lachal S,Shulkes A,Baldwin GS

    更新日期:2012-02-15 00:00:00

  • Histamine H1 receptor-induced Ca2+ mobilization and prostaglandin E2 release in human gingival fibroblasts. Possible role of receptor-operated Ca2+ influx.

    abstract::Stimulation of human gingival fibroblasts with histamine elicited an increase in the intracellular concentration of free calcium ([Ca2+]i) and the formation of inositol 1,4,5-trisphosphate (InsP3) in a concentration- and time-dependent manner. The histamine-induced increase in [Ca2+]i was attenuated completely by chlo...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(96)00417-0

    authors: Niisato N,Ogata Y,Furuyama S,Sugiya H

    更新日期:1996-10-11 00:00:00

  • Evaluation of loratadine as an inducer of liver microsomal cytochrome P450 in rats and mice.

    abstract::The non-sedating anti-histamine, loratadine [ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin- 11-ylidene-1-piperidinecarboxylate], was administered orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 weeks. The effects of these treatments on liver microsomal cytochro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90176-j

    authors: Parkinson A,Clement RP,Casciano CN,Cayen MN

    更新日期:1992-05-28 00:00:00

  • Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment.

    abstract::Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric (Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of pharmacological effects including antitumor, antiinflammatory, and antiinfectious activities. Although its precise mode of action remains elusive, curcumin has been ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00251-7

    authors: Sikora E,Bielak-Zmijewska A,Piwocka K,Skierski J,Radziszewska E

    更新日期:1997-10-15 00:00:00

  • Kinetics of human thrombin inhibition by two novel peptide inhibitors (Hirunorm IV and Hirunorm V).

    abstract::A study on the kinetics of human thrombin inhibition by two novel synthetic peptides (Hirunorm IV and Hirunorm V) and a comparison with recombinant hirudin and a commonly used thrombin inhibitor, Hirulog-1, are reported. The dissociation constants for Hirunorm IV and Hirunorm V were determined by varying the concentra...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(96)00388-7

    authors: Cappiello M,Vilardo PG,Lippi A,Criscuoli M,Del Corso A,Mura U

    更新日期:1996-10-25 00:00:00

  • Evidence for the shuttle model for Gs alpha activation of adenylyl cyclase.

    abstract::Knowledge of the nature of the interaction between the stimulatory G protein (Gs) and the adenylyl cyclase catalytic unit (C) is essential for interpreting the effects of Gs mutations and expression levels on cellular response to a wide variety of hormones, drugs, and neurotransmitters. It has been proposed that beta-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(97)00148-2

    authors: Krumins AM,Lapeyre JN,Clark RB,Barber R

    更新日期:1997-07-01 00:00:00

  • The role of thiol oxidation in Cobalt(II)-induced toxicity in hamster lung.

    abstract::Exposure of lung tissue to Co(II) ions both in vivo and in vitro results in toxicity, a relatively early event of which is the oxidation of cellular glutathione. In this study we have attempted to delineate the relationship between this oxidation of glutathione and the subsequent development of cellular dysfunction. S...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90573-2

    authors: Lewis CP,Demedts M,Nemery B

    更新日期:1992-02-04 00:00:00

  • Effect of anthracyclines on phospholipase A2 activity and prostaglandin E2 production in rat gastric mucosa.

    abstract::The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90509-u

    authors: Grataroli R,Leonardi J,Chautan M,Lafont H,Nalbone G

    更新日期:1993-08-03 00:00:00

  • The interactions of milacemide with monoamine oxidase.

    abstract::The interactions of the anticonvulsant drug milacemide (2-n-pentylaminoacetamide) with rat liver mitochondrial monoamine oxidases-A and -B have been studied. The compound acts as a substrate for the B-form of the enzyme, with an apparent Km value of 49 +/- 4.7 microM and a Vmax value of 1.1 +/- 0.2 nmol/min/mg. It is ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90123-6

    authors: O'Brien EM,Tipton KF,McCrodden JM,Youdim MB

    更新日期:1994-02-11 00:00:00

  • Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3.

    abstract::Tachykinin NK receptors (NKRs) differ to a large degree among species with respect to their affinities for small molecule antagonists. The aims of the present study were to clone NKRs from gerbil (NK2R and NK3R) and dog (NK1R, NK2R and NK3R) in which the sequence was previously unknown and to investigate the potency o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2009.01.020

    authors: Leffler A,Ahlstedt I,Engberg S,Svensson A,Billger M,Oberg L,Bjursell MK,Lindström E,von Mentzer B

    更新日期:2009-05-01 00:00:00

  • Inhibition of fatty acid biosynthesis by bezafibrate in different rat cells.

    abstract::Bezafibrate is one of the main drugs used in the treatment of human hyperlipemic diseases. Its action on the biosynthesis of fatty acids has been studied and the following conclusions have been drawn: (1) Lipogenesis from glucose is inhibited in hepatocytes and adipocytes isolated from "refed" rats previously treated ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(89)90095-6

    authors: Villanueva C,Fabregat I,Machado A

    更新日期:1989-08-01 00:00:00

  • Epithelial peptide antibiotics.

    abstract::Surfaces of higher eukaryotes such as plants, invertebrates, and vertebrates, including humans, are normally covered with microorganisms but usually are not infected by them. The reason, apart from physical barriers, is the production of gene-encoded antimicrobial peptides by epithelial cells. Many novel antimicrobial...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/s0006-2952(98)00226-3

    authors: Schröder JM

    更新日期:1999-01-15 00:00:00

  • Preparation and characterization of subcellular fractions from the liver of the Northern Pike, Esox lucius.

    abstract::The present study was designed to prepare and characterize subcellular fractions from the liver of the Northern pike (Esox lucius), with special emphasis on the preparation of microsomal fractions suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90371-9

    authors: Balk L,Meijer J,Bergstrand A,Aström A,Morgenstern R,Seidegård J,DePierre JW

    更新日期:1982-04-15 00:00:00

  • Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries.

    abstract::Nuclear factor-kappaB (NFKB) is a transcription factor with a pivotal role in inducing genes involved in physiological processes as well as in the response to injury and infection. A model has been proposed whereby the diverse agents that activate NFkappaB do so by increasing oxidative stress within the cell. Activati...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/s0006-2952(99)00296-8

    authors: Bowie A,O'Neill LA

    更新日期:2000-01-01 00:00:00

  • GABAB receptor phosphorylation regulates KCTD12-induced K⁺ current desensitization.

    abstract::GABAB receptors assemble from GABAB1 and GABAB2 subunits. GABAB2 additionally associates with auxiliary KCTD subunits (named after their K(+) channel tetramerization-domain). GABAB receptors couple to heterotrimeric G-proteins and activate inwardly-rectifying K(+) channels through the βγ subunits released from the G-p...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2014.07.013

    authors: Adelfinger L,Turecek R,Ivankova K,Jensen AA,Moss SJ,Gassmann M,Bettler B

    更新日期:2014-10-01 00:00:00

  • Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells.

    abstract::cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(01)00748-1

    authors: Lee RH,Song JM,Park MY,Kang SK,Kim YK,Jung JS

    更新日期:2001-10-15 00:00:00