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-doxorubicin, 4'-deoxy-doxorubicin, iododoxorubicin, 3'-(3-methoxymorpholino)-doxorubicin (FCE23762) and 4-demethoxy-daunorubicin) into K562 cells sensitive and resistant (K562/DNR) to daunorubicin. The K562/DNR subline expresses Pgp at the membrane surface, whereas its sensitive counterpart does not. Laser flow cytometry was used to quantitate intracellular anthracycline content. Uptake of daunorubicin, doxorubicin, 4'-epi-doxorubicin, and 4'-deoxy-doxorubicin was minimal in the K562/DNR subline as compared to their uptake in sensitive cells. On the contrary, iododoxorubicin, FCE23762, and 4-demethoxy-daunorubicin accumulate to nearly the same extent into sensitive and resistant K562 cells. Growth inhibition data indicated that the resistance factor for iododoxorubicin, FCE23762, and 4-demethoxy-daunorubicin is markedly decreased as compared to the other drugs. Fluorescence measurements were carried out to determine the kinetic parameters associated with the influx and efflux of the drugs into and out of K562 cells. Kinetic data indicated that iododoxorubicin, FCE23762, and 4-demethoxy-daunorubicin are not actively rejected from resistant cells, suggesting that they are poor substrates for Pgp-mediated transport. This observation is related to their ability to overcome the multidrug-resistant phenotype of K562/DNR cells in vitro.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Praet M,Stryckmans P,Ruysschaert JMdoi
10.1016/0006-2952(96)00042-1subject
Has Abstractpub_date
1996-05-17 00:00:00pages
1341-8issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(96)00042-1journal_volume
51pub_type
杂志文章abstract::The data reported suggest that--following initiation of lipid peroxidation--membrane protein thiols can be attacked by lipid-derived radicals and/or reactive, lipid-soluble aldehydes like 4-hydroxynonenal and other hydroxyalkenals originated within the lipid core of cell membranes, resulting in a membrane protein thio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90666-s
更新日期:1991-04-15 00:00:00
abstract::The response and engagement of host normal tissues in malignant disease are major factors in therapeutic resistance. Physically, solid tumors have regions of hypoxia and acidosis. These physical stresses can lead to a more aggressive malignant phenotype through activation of HIF, GLUT-1, carbonic anhydrase IX, and sub...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.01.006
更新日期:2009-06-01 00:00:00
abstract::The cytoprotective effect of the natural dietary constituent indole-3-carbinol (I-3-C) on carbon tetrachloride (CCl4) mediated hepatotoxicity in mice was examined. I-3-C pretreatment by gavage 1 hr prior to intraperitoneal injection of CCl4 produced a 63% decrease in CCl4-mediated centrolobular necrosis and a related ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90737-x
更新日期:1988-01-15 00:00:00
abstract::Selective and marked 3-hydroxylase deficiency of lidocaine and its N-deethylated metabolite, MEGX, were observed in male and female DA rats. These findings suggest that cytochrome P450 isozymes metabolizing debrisoquine may be involved in the 3-hydroxylations of lidocaine and MEGX in rats and humans. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90333-z
更新日期:1991-07-15 00:00:00
abstract::The metabolism of alpha,alpha,beta,beta- tetradeutero -N,N -dimethyltryptamine ( D4DMT ) in rat brain in vivo as a function of time and dose was examined. Quantification of D4DMT and its respective deutero-metabolites was accomplished using gas chromatographic/mass spectrometric/selected ion monitoring/isotope dilutio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90404-0
更新日期:1984-05-01 00:00:00
abstract::We have investigated whether or not the cellular content of reactive platinum, aside from total cellular and DNA-bound platinum, is a measure of the growth inhibitory potential of a given platinum complex. Human MCF-7 breast cancer cells, after treatment with cisplatin [cis-diamminedichloroplatinum(II)] and several 1,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(96)00106-2
更新日期:1996-07-12 00:00:00
abstract::The serine esterase inhibitor diisopropyl fluorophosphate (DFP) had been reported previously to inhibit IgE-dependent histamine release. Recently, it has been demonstrated that lower concentrations of DFP enhance IgE-dependent histamine release and inhibit desensitization. This manuscript describes the abilities of se...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90686-6
更新日期:1986-12-01 00:00:00
abstract::N,N-Dimethyl-D-erythro-sphingosine (DMS) is the N-methyl derivative of sphingosine; both are activators of sphingosine-dependent protein kinases. The aim of this work was to study the effect of DMS on cytosolic calcium and intracellular pH (pHi) in human T lymphocytes. The variations of calcium and pH were determined ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01519-8
更新日期:2003-02-01 00:00:00
abstract::Amodiaquine, a 4-aminoquinoline antimalarial, has been associated with hepatitis and agranulocytosis in humans. Drug hypersensitivity reactions, especially agranulocytosis, have been attributed to reactive intermediates generated by the oxidants discharged from stimulated polymorphonuclear leucocytes (PMN). The metabo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)00236-s
更新日期:1995-09-28 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90561-1
更新日期:1985-08-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90319-9
更新日期:1986-05-15 00:00:00
abstract::The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90127-9
更新日期:1986-05-01 00:00:00
abstract::Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the replet...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90757-4
更新日期:1986-12-15 00:00:00
abstract::The cytotoxicity anti-tumour intercalating agents such as the anthraquinone mitoxantrone is thought to relate to DNA binding and the trapping of DNA topoisomerase II complexes on cellular DNA. We have studied the uptake, nuclear location, DNA binding mode and DNA damaging capacity of mitoxantrone in a small cell lung ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90237-f
更新日期:1990-11-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.113927
更新日期:2020-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2009.11.012
更新日期:2010-04-01 00:00:00
abstract::Ibuprofen and related 2-arylpropanoic acid (2-APA) drugs are often given as a racemic mixture and the R-enantiomers undergo activation in vivo by metabolic chiral inversion. The chiral inversion pathway consists of conversion of the drug to the coenzyme A ester (by an acyl-CoA synthetase) followed by chiral inversion ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.08.067
更新日期:2013-12-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00531-7
更新日期:2001-03-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00544-6
更新日期:2003-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90732-k
更新日期:1991-07-05 00:00:00
abstract::Tianeptine is a new tricyclic antidepressant which is metabolized mainly by beta-oxidation of its heptanoic side chain. We determined the effects of tianeptine on the mitochondrial oxidation of natural fatty acids in mice. In vitro, tianeptine (0.5 mM) inhibited by only 32% the formation of beta-oxidation products fro...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90580-7
更新日期:1989-11-01 00:00:00
abstract::The microsomal brush-border fraction of rat renal tissue contains enzymatic activity, optimally active at pH 9, that is capable of degrading human myelin basic protein (BP) peptide 43-88. In the present study, this degradation and the effect on it of selected drugs and hormones were examined further. Of the substances...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90500-3
更新日期:1985-04-15 00:00:00
abstract::Two methods avoiding the widespread technique of collagenase perfusion have been employed to study the regulation of total cytochrome P450 content in rat hepatocyte culture. One technique required the perfusion of the liver with the chelating agent EDTA to dissociate the parenchymal cells prior to culture. Over a peri...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90283-o
更新日期:1992-01-22 00:00:00
abstract::The cytoprotective effects of propylthiouracil (PTU) were studied in rats treated with the hepatotoxin D-galactosamine (D-GNH2). Five days of PTU pretreatment prior to D-GNH2 caused hypothyroidism and a significant reduction in liver injury as assessed by serum transaminase levels. When PTU was administered as a singl...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90110-2
更新日期:1984-11-01 00:00:00
abstract::In this study, the basis for the diminished capacity of CYP2D6.17 to metabolise CYP2D6 substrate drugs and the possible implications this might have for CYP2D6 phenotyping studies and clinical use of substrate drugs were investigated in vitro. Enzyme kinetic analyses were performed with recombinant CYP2D6.1, CYP2D6.2,...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01351-5
更新日期:2002-11-01 00:00:00
abstract::Agonist-stimulated phosphoinositide metabolism plays a central role in pharmacomechanical coupling in airways smooth muscle (ASM). In many other tissues and cells, most noteably excitable cells, membrane depolarization or an increase in intracellular Ca2+ ([Ca2+]i) generated by inositol 1,4,5-trisphosphate (Ins(1,4,5)...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90252-6
更新日期:1994-06-15 00:00:00
abstract::The protein tyrosine kinase (PTK) inhibitor genistein has been demonstrated to inhibit platelet-activating factor-stimulated prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells (Glaser et al., J Biol Chem 265: 8658-8664, 1990). Therefore, the role of PTK in eicosanoid bio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90147-o
更新日期:1993-02-09 00:00:00
abstract::When human saliva obtained after cigarette smoking was incubated in the presence of tryptamine, the formation of 1,2,3,4-tetrahydro-beta-carboline (TBC) and 1-methyl-1,2,3,4-tetrahydro-beta-carboline (MTBC) was observed in a short time. After incubation with tryptamine (2.5 micrograms/microliter) for 10 min, the conce...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02068-3
更新日期:1995-12-22 00:00:00
abstract::Engelbreth-Holm-Swarm (EHS) tumor cells were utilized as a model for investigating the production of basement membrane components. These cells contain two immunologically distinct NADPH-dependent reductases, aldose reductase (EC 1.1.1.21) and aldehyde reductase (EC 1.1.1.2), which were purified to apparent homogeneity...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90049-q
更新日期:1990-02-01 00:00:00
abstract::The Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 (LY2), has been previously reported to inhibit nuclear factor κB (NFκB) activity, in a PI3K-independent mechanism. The goals of the current research were to determine the specificity of LY2 regarding NFκB subunits, and to identify relevant modulation of cyto...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.09.025
更新日期:2012-01-01 00:00:00