Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARgamma.

Abstract:

:Deoxyelephantopin (ESD) was reported to potentiate apoptosis, inhibit invasion and abolish osteoclastogenesis but no target protein was disclosed. Here, we discovered that ESD could significantly inhibit the proliferation of different cancer cells and induce apoptosis and cell cycle arrest at G(2)/M phase in HeLa cell. Moreover, biochemical and biophysical assays revealed that ESD acted as a specific partial agonist against PPARgamma. Molecular docking with site-directed mutagenesis analyses indicated that ESD functioned as a partial agonist of PPARgamma by adopting a distinct binding mode to PPARgamma compared with rosiglitazone. The PPARgamma knockdown results indicated that the inhibition of ESD against the cancer cell proliferation is more possibly through PPARgamma-independent pathway and our findings might supply potent binding features for ESD/PPARgamma interaction at atomic level, and shed light on the potential acting target information for this natural compound.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Zou G,Gao Z,Wang J,Zhang Y,Ding H,Huang J,Chen L,Guo Y,Jiang H,Shen X

doi

10.1016/j.bcp.2007.11.021

subject

Has Abstract

pub_date

2008-03-15 00:00:00

pages

1381-92

issue

6

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(07)00770-8

journal_volume

75

pub_type

杂志文章
  • Mouse N-acetyltransferase type 2, the homologue of human N-acetyltransferase type 1.

    abstract::There is increasing evidence that human arylamine N-acetyltransferase type 1 (NAT1, EC 2.3.1.5), although first identified as a homologue of a drug-metabolising enzyme, appears to be a marker in human oestrogen receptor positive breast cancer. Mouse Nat2 is the mouse equivalent of human NAT1. The development of mouse ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2007.12.012

    authors: Kawamura A,Westwood I,Wakefield L,Long H,Zhang N,Walters K,Redfield C,Sim E

    更新日期:2008-04-01 00:00:00

  • Prevention of microsomal production of hydroxyl radicals, but not lipid peroxidation, by the glutathione-glutathione peroxidase system.

    abstract::The glutathione-glutathione peroxidase system is an important defense against oxidative stress. The ability of this system to protect against iron-catalyzed microsomal production of hydroxyl radicals [oxidation of 4-methylmercapto-2-oxo-butyrate (KMBA)] and lipid peroxidation was evaluated. When rat liver cytosol was ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90172-3

    authors: Beloqui O,Cederbaum AI

    更新日期:1986-08-15 00:00:00

  • In vitro and in vivo inhibition by benserazide of clorgyline-resistant amine oxidases in rat cardiovascular tissues.

    abstract::Bernserazide (D,L-serine 2-[2,3,4-trihydroxybenzyl]-hydrazide) as been shown to inhibit the clorgyline-resistant amine oxidase (CRAO) activities which metabolize benzylamine in homogenates of rat aorta, heart and brown adipose tissue. In vitro studies showed a concentration- and time-dependent inhibition of CRAO in he...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90037-5

    authors: Lyles GA,Callingham BA

    更新日期:1982-04-01 00:00:00

  • Venom-derived modulators of epilepsy-related ion channels.

    abstract::Epilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapse...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2020.114043

    authors: Chow CY,Absalom N,Biggs K,King GF,Ma L

    更新日期:2020-11-01 00:00:00

  • Comparative intracellular uptake of adriamycin and 4'-deoxydoxorubicin by non-small cell lung tumor cells in culture and its relationship to cell survival.

    abstract::4'-Deoxydoxorubicin (4'-deoxy) is a new adriamycin analogue with a similar spectrum of antitumour activity but is significantly more lipophilic than the parent compound. We report the kinetics and uptake of the two drugs by human non-small cell lung tumour cells in monolayer culture and the relationship between intrac...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90195-4

    authors: Kerr DJ,Kerr AM,Freshney RI,Kaye SB

    更新日期:1986-08-15 00:00:00

  • Strain differences in susceptibility of normal and diabetic rats to acetaminophen hepatotoxicity.

    abstract::The effects of streptozotocin (STZ)-induced diabetes on acetaminophen metabolism and hepatotoxicity in male Sprague-Dawley (SD) and Long Evans Hooded (LEH) rats were compared. In agreement with earlier studies, normal SD rats were more resistant to acetaminophen-induced hepatic necrosis than normal LEH rats. In contra...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90368-0

    authors: Price VF,Jollow DJ

    更新日期:1986-02-15 00:00:00

  • Cellular uptake, cytotoxicity, and transport kinetics of anthracyclines in human sensitive and multidrug-resistant K562 cells.

    abstract::Multidrug resistance in tumor cells is often associated with the presence of an approximately 170 kDa plasma membrane glycoprotein (Pgp) that acts as a drug-efflux pump and decreases intracellular antitumor drug concentration. We measured the uptake of seven anthracyclines (daunorubicin, doxorubicin, 4'-epi-doxorubici...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(96)00042-1

    authors: Praet M,Stryckmans P,Ruysschaert JM

    更新日期:1996-05-17 00:00:00

  • Effect of chronic hypoxia on acetaminophen metabolism in the rat.

    abstract::The effect of chronic hypoxia (10.5% O2 for 8-9 days) on acetaminophen metabolism was studied in vivo or in isolated cell or microsomal systems. Results from in vivo studies with oral administration of acetaminophen showed that in hypoxic rats, the plasma appearance of the drug was delayed and the plasma half-life was...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(91)90285-d

    authors: Aw TY,Shan XQ,Sillau AH,Jones DP

    更新日期:1991-08-08 00:00:00

  • Posttranslationally modified ornithine decarboxylase may regulate RNA polymerase I activity.

    abstract::Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(82)90614-1

    authors: Russell DH,Manen CA

    更新日期:1982-11-01 00:00:00

  • Uptake and cytotoxicity of novel nitroimidazole-polyamine conjugates in Ehrlich ascites tumour cells.

    abstract::A number of tumour cells, including Ehrlich ascites tumour cells (EATC), possess a polyamine uptake system which selectively accumulates endogenous polyamines and structurally related compounds by an active energy dependent system(s). We suggest that it may be possible to utilize this uptake system to target certain c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(92)90241-a

    authors: Holley J,Mather A,Cullis P,Symons MR,Wardman P,Watt RA,Cohen GM

    更新日期:1992-02-18 00:00:00

  • Potentiation of mitochondrial Ca2+ sequestration by taurine.

    abstract::The effects of taurine (2-aminoethanesulphonic acid) and its analogues, 2-aminoethylarsonic acid, 2-hydroxyethanesulphonic (isethionic) acid, 3-aminopropanesulphonic acid, 2-aminoethylphosphonic acid, and N,N-dimethyltaurine, were studied on the transport of Ca2+ by mitochondria isolated from rat liver. Taurine enhanc...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(99)00183-5

    authors: Palmi M,Youmbi GT,Fusi F,Sgaragli GP,Dixon HB,Frosini M,Tipton KF

    更新日期:1999-10-01 00:00:00

  • Changes in the biliary excretion of organic anions following exhaustive exercise in rats.

    abstract::The effect of exhaustive exercise on the hepatobiliary transport of organic anions was investigated in rats. Animals were run on a rodent treadmill at 24 m/min up a 12% grade (152 +/- 15 min). Exercise resulted in significant hypoglycaemia (-46%) and increased plasma levels of lactate (+12%), together with a marked re...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(90)90094-2

    authors: Villa JG,Collado PS,Almar MM,Gonzalez J

    更新日期:1990-12-01 00:00:00

  • Increased Akt protein expression is associated with decreased ceramide content in skeletal muscle of troglitazone-treated mice.

    abstract::Although it is generally believed that thiazolidinediones ameliorate insulin resistance by lowering circulating free fatty acids, direct effects of these drugs in skeletal muscle may also contribute to their antidiabetic action. We report that troglitazone administration to mice for 1 day increased the protein express...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2005.01.015

    authors: Planavila A,Alegret M,Sánchez RM,Rodríguez-Calvo R,Laguna JC,Vázquez-Carrera M

    更新日期:2005-04-15 00:00:00

  • Effects of gramine on energy metabolism of rat and bovine mitochondria.

    abstract::The indole alkaloid gramine is found in several plant families. Its effects on mammalian mitochondria and submitochondrial particles were studied. Low concentrations of gramine slightly stimulated basal electron transport, totally inhibited the Ca2+-induced respiratory control and partially abolished the enhancement o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90596-3

    authors: Niemeyer HM,Roveri OA

    更新日期:1984-10-01 00:00:00

  • Effect of staurosporine on transcription factor NF-kappaB in human keratinocytes.

    abstract::Activation of the transcription factor NF-kappaB is known to be important in the regulated expression of a large number of pro-inflammatory genes including interleukin-8 (IL-8). Previously, we showed that the protein kinase inhibitor staurosporine potentiates IL-1-stimulated IL-8 production in human keratinocytes. Mor...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(98)00117-8

    authors: Chabot-Fletcher M,Breton JJ

    更新日期:1998-07-01 00:00:00

  • Quercetin decreases intracellular GSH content and potentiates the apoptotic action of the antileukemic drug arsenic trioxide in human leukemia cell lines.

    abstract::Arsenic trioxide (ATO) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, but successful application of this agent may occasionally require the use of sensitizing strategies. The present work demonstrates that the flavonoids quercetin and chrysin cooperate with ATO to induce apoptosis...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.bcp.2008.02.007

    authors: Ramos AM,Aller P

    更新日期:2008-05-15 00:00:00

  • Induction of human neutrophil apoptosis by nitric oxide donors: evidence for a caspase-dependent, cyclic-GMP-independent, mechanism.

    abstract::This study investigated the regulatory effects of the major inflammatory mediator, nitric oxide (NO), on human neutrophil apoptosis in vitro. Co-culture of human neutrophils with the NO donors GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3-(3,4-dichlorophenyl)-chloride) (10-100 microM) and 3-morpholino-sydnonimine (SIN-1) ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(99)00329-9

    authors: Ward C,Wong TH,Murray J,Rahman I,Haslett C,Chilvers ER,Rossi AG

    更新日期:2000-02-01 00:00:00

  • Covalent coupling of doxorubicin in protein microspheres is a major determinant of tumour drug disposition.

    abstract::Doxorubicin is shown to be present in albumin microspheres (10-40 microns) in two forms: the native drug and a fraction of drug covalently coupled to the protein matrix probably via glutaraldehyde. Upon trypsin digestion the fraction covalently coupled is released and can be resolved from native doxorubicin by high pe...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(91)90123-m

    authors: Cummings J,Willmott N,Marley E,Smyth J

    更新日期:1991-06-15 00:00:00

  • Effects of the chrysotherapeutic agents auranofin and gold sodium thiomalate on hepatic and renal drug metabolism and heme metabolism.

    abstract::These studies were designed to investigate the effects of the chrysotherapeutic agents auranofin and myochrysine (GST) on hepatic and renal drug-metabolizing enzymes and heme metabolism. Male Sprague-Dawley rats were either administered a single dose of auranofin (17, 34, or 68 mg/kg, p.o.) or administered daily doses...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(86)90386-2

    authors: Leonard TB,Graichen ME,Dahm LJ,Dent JG

    更新日期:1986-09-15 00:00:00

  • Nature and role of xenobiotic metabolizing esterases in rat liver, lung, skin and blood.

    abstract::In the present study, the distribution and nature of esterases in the rat which hydrolysed fluazifop-butyl, carbaryl, paraoxon and phenylacetate were investigated. Vmax and Km values for the hydrolysis reactions were determined. Fluazifop-butyl was hydrolysed to fluazifop by rat liver (Vmax mumol/min/g microsomes 6.2 ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90373-5

    authors: McCracken NW,Blain PG,Williams FM

    更新日期:1993-01-07 00:00:00

  • Effect of acetyl-L-carnitine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.

    abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is believed to induce neurotoxicity by inhibiting mitochondrial oxidative metabolism, whereas acetyl-L-carnitine (ALC) facilitates this process by transporting fatty acids into mitochondria for beta oxidation. We investigated whether large doses of ALC given by gavag...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90034-t

    authors: Harik SI,Hritz MA

    更新日期:1993-05-25 00:00:00

  • Kinetics of methotrexate binding to dihydrofolate reductase from Neisseria gonorrhoeae.

    abstract::The kinetics of methotrexate inhibition of dihydrofolate reductase from Neisseria gonorrhoeae have been investigated. Methotrexate was shown to be a tight-binding inhibitor (Kt = 13 pM) competitive with dihydrofolate. However, "stoichiometric" or "pseudoirreversible" inhibition could not be demonstrated. Progress curv...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(84)90579-3

    authors: Baccanari DP,Tansik RL

    更新日期:1984-07-01 00:00:00

  • Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms.

    abstract::Extracellular ATP suppressed the growth of HL-60 leukemia cells and induced their differentiation as revealed by N-formyl-methionyl-leucyl-phenylalanine-induced beta-glucuronidase release. ATP degraded to ADP, AMP, and adenosine, and the effect of ATP on cell growth was mimicked by these metabolites added to the cultu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(00)00465-2

    authors: Conigrave AD,van der Weyden L,Holt L,Jiang L,Wilson P,Christopherson RI,Morris MB

    更新日期:2000-12-01 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

  • Behavioural and neurochemical interactions between chronic reserpine and chronic antidepressants. A possible model for the detection of atypical antidepressants.

    abstract::Chronic treatment with a low dose of reserpine (0.1 mg/kg) caused rats to become hyperactive in the "open field" apparatus. When mianserin (5 mg/kg) or the selective serotonin uptake inhibitor ORG. 6582 (5 mg/kg) was chronically administered in combination with reserpine, the hyperactivity was attenuated. Both antidep...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(83)90329-5

    authors: Jancsár SM,Leonard BE

    更新日期:1983-05-15 00:00:00

  • Molecular mechanism of L-DNase II activation and function as a molecular switch in apoptosis.

    abstract::The discovery of caspase activation counts as one of the most important finds in the biochemistry of apoptosis. However, targeted disruption of caspases does not impair every type of apoptosis. Other proteases can replace caspases and several so called "caspase independent" pathways are now described. Here we review o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.bcp.2008.07.039

    authors: Torriglia A,Leprêtre C,Padrón-Barthe L,Chahory S,Martin E

    更新日期:2008-12-01 00:00:00

  • New sulfonated distamycin A derivatives with bFGF complexing activity.

    abstract::Tumor-induced neoangiogenesis is an essential event for solid tumor growth. Therefore, a compound able to block angiogenesis-promoting factors could have antitumor activity. The polysulfonated naphthylurea suramin is hypothesized to have this mode of action. A series of sulfonated distamycin A derivatives have been sy...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(94)90020-5

    authors: Ciomei M,Pastori W,Mariani M,Sola F,Grandi M,Mongelli N

    更新日期:1994-01-20 00:00:00

  • Degradation of endomorphin-2 at the supraspinal level in mice is initiated by dipeptidyl peptidase IV: an in vitro and in vivo study.

    abstract::Endomorphin-2 (Tyr-Pro-Phe-PheNH(2)) was discovered as an endogenous ligand for the mu-opioid receptor. The physiological function of endomorphin-2 as a neurotransmitter or neuromodulator may cease through the rapid enzymatic process in the synapse of brain, as for other neuropeptides. The present study was conducted ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0006-2952(03)00391-5

    authors: Sakurada C,Sakurada S,Hayashi T,Katsuyama S,Tan-No K,Sakurada T

    更新日期:2003-08-15 00:00:00

  • Sex differences in the diabetes-induced modulation of rat hepatic cytochrome P450 proteins.

    abstract::Sex differences in the diabetes-induced changes in hepatic cytochrome P450 proteins were investigated in rats treated with streptozotocin. Changes in specific cytochrome P450 proteins were monitored using diagnostic substrates and immunologically utilizing specific polyclonal antibodies. When expressed in terms of nmo...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90066-6

    authors: Barnett CR,Rudd S,Flatt PR,Ioannides C

    更新日期:1993-01-26 00:00:00

  • Species-dependent differences in the biochemical effects and metabolism of 5-benzylacyclouridine.

    abstract::The pharmacokinetics and biochemical effects of the uridine phosphorylase (UrdPase) inhibitor 5-benzylacyclouridine (BAU) were investigated in the mouse, rat and monkey. Following i.p. administration of BAU (30 mg/kg) in the mouse and i.v. administration in the rat and monkey, initial BAU plasma half-life values were ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章

    doi:10.1016/0006-2952(93)90390-i

    authors: Davis ST,Joyner SS,Chandrasurin P,Baccanari DP

    更新日期:1993-01-07 00:00:00