Abstract:
:The proteasome inhibitor bortezomib is currently an important drug for treatment of relapsed and refractory multiple myeloma (MM) and for elderly patients. However, cells from some patients show resistance to bortezomib. We have evaluated the possibility of improving bortezomib therapy with Apo2L/TRAIL, a death ligand that induces apoptosis in MM but not in normal cells. Results indicate that cotreatment with low doses of bortezomib significantly increased apoptosis of MM cells showing partial sensitivity to Apo2L/TRAIL. Bortezomib treatment did not significantly alter plasma membrane amount of DR4 and DR5 but increased Apo2L/TRAIL-induced caspase-8 and caspase-3 activation. Apo2L/TRAIL reverted bortezomib-induced up-regulation of beta-catenin, Mcl-1 and FLIP, associated with the enhanced cytotoxicity of combined treatment. More important, some cell lines displaying resistance to bortezomib were sensitive to Apo2L/TRAIL-induced apoptosis. A cell line made resistant by continuous culture of RPMI 8226 cells in the presence of bortezomib (8226/7B) was highly sensitive to Apo2L/TRAIL-induced apoptosis. Moreover, RPMI 8226 cells overexpressing Mcl-1 (8226/Mcl-1) or Bcl-x(L) (8226/Bcl-x(L)) also showed enhanced resistance to bortezomib, but co-treatment with Apo2L/TRAIL reverted this resistance. These results indicate that Apo2L/TRAIL can cooperate with bortezomib to induce apoptosis in myeloma cells and can be an useful adjunct for MM therapy.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Balsas P,López-Royuela N,Galán-Malo P,Anel A,Marzo I,Naval Jdoi
10.1016/j.bcp.2008.11.024subject
Has Abstractpub_date
2009-03-01 00:00:00pages
804-12issue
5eissn
0006-2952issn
1873-2968pii
S0006-2952(08)00827-7journal_volume
77pub_type
杂志文章abstract::Pretreatment of NG108-15 cells with 0.03-25 microM prostaglandin E1 (PGE1) produced decreases in the maximal stimulation of adenylate cyclase activity produced by iloprost, N-ethylcarboxamidoadenosine and sodium fluoride. The rate of desensitization to all three agents was dependent on the concentration of PGE1 used, ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90405-7
更新日期:1994-03-15 00:00:00
abstract::The effect of macrophage supernatant on the recovery of wounds induced in rat gastric epithelial RGM1 monolayers was investigated. The repair of wounds induced in the monolayers of RGM1 cells was accelerated time-dependently by 10 ng/mL of transforming growth factor-alpha (TGF-alpha). TGF-alpha also significantly stim...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(99)00202-6
更新日期:1999-10-01 00:00:00
abstract::Flunarizine, a calcium (Ca2+)-entry blocker, selective for vascular tissues, inhibits in a concn-dependent way the contraction of isolated rat caudal artery preparations induced by mediators derived from thrombin-stimulated rat platelets. This inhibition is slow in onset and is of prolonged duration. Specific measurem...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90574-9
更新日期:1983-03-01 00:00:00
abstract::Cyclic nucleotide phosphodiesterases (PDEs) are the only enzymes that inactivate intracellular cyclic AMP (cAMP). Because the functions of T-lymphocytes are modulated by cAMP levels, the isozymes of PDE in these cells are potential targets for new drugs designed to modify the body's immunity through selective alterati...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90047-9
更新日期:1991-07-25 00:00:00
abstract::Forskolin, a diterpene compound isolated from the roots of Coleus forskohlii, activates adenylate cyclase in membranes from a variety of mammalian tissues. We found that forskolin (10(-7) to 3 X 10(-5) M) caused a concentration-related inhibition of IgE-mediated release of histamine and peptide leukotriene C4 (LTC4) f...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90377-7
更新日期:1987-01-01 00:00:00
abstract::Neutrophil serine proteases (NSPs), including elastase, proteinase 3 and cathepsin G, play critical roles in the pathogenesis of chronic inflammatory lung diseases. The release of excess NSPs leads to the destruction of lung tissue and an overexuberant, sustained inflammatory response. Antiproteases could be valuable ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2012.03.009
更新日期:2012-06-15 00:00:00
abstract::The in vitro metabolic ketone reduction of warfarin and its 4'-analogues acenocoumarol (4'-nitrowarfarin) and 4'-chlorowarfarin has been investigated using microsomal and cytosolic fractions of several species. Both subcellular fractions showed ketone reductase activity. The cytosolic fractions, in most species, exhib...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90635-7
更新日期:1989-10-01 00:00:00
abstract::Adenosine potentiates mouse bone marrow-derived mast cell mediator release by a mechanism that appears to involve cell surface adenosine receptors. In an attempt to explore possible interactions between G proteins and adenosine receptors, mast cells were incubated with activated pertussis toxin, an agent that ADP-ribo...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90088-3
更新日期:1988-10-15 00:00:00
abstract::Naturally occurring amino acid substitutions conferring resistance to methotrexate (MTX) have been reported previously at codon positions 22 (leu-->arg, phe) and 31 (phe-->ser, trp) of mammalian dihydrofolate reductases (DHFR). To explore the character of other substitutions, a polymerase chain reaction (PCR)-assisted...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90393-x
更新日期:1994-03-29 00:00:00
abstract::Ischemia/reperfusion (I/R) injury constitutes a major reason for failure of liver surgeries and transplantation. I/R injury is more severe in steatotic livers and limits their use in transplantation. Here, we present a novel and selective Toll-like receptor 9 (TLR9) antagonist COV08-0064 and test its potential to prot...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.05.003
更新日期:2016-07-15 00:00:00
abstract::5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions. The pathophysiological effects of LTs are considered to be prevented by 5-LO inhibitors. In this study we presen...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.10.012
更新日期:2012-01-15 00:00:00
abstract::Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.09.004
更新日期:2006-12-15 00:00:00
abstract::3H-(+/-) propranolol and 125I-(+/-) cyanopindolol have been used to characterize beta adrenoceptors of liver, lung, kidney and heart of rat. Two main binding parameters, KD and Bmax were measured using either cells, homogenates or plasma membranes of each organ (except heart). Results show that the most accurate deter...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90365-9
更新日期:1983-11-15 00:00:00
abstract::Administration of phenobarbital, a known inducer of glutathione S-transferase activity in rat liver, failed to stimulate sulfobromophthalein (BSP) conjugation by liver cytosol in hamsters. The latter displayed poor ability to conjugate this substrate, despite very high glutathione-conjugating activity with the broad-s...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90540-5
更新日期:1987-08-15 00:00:00
abstract::Specific binding of 35S-t-butylbicyclophosphorothionate (TBPS) was studied in synaptosomal membranes of rat cerebral cortex under nonequilibrium conditions. TBPS binding proved to be suitable for the characterization of not only the efficacy but also the potency of benzodiazepine (BZ) receptor ligands in vitro. Five B...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90581-3
更新日期:1988-06-01 00:00:00
abstract::Angiogenesis, the development of neovessels from pre-existing vessels, is obligatory for solid tumors survival, growth, invasion, and metastasis. Many anti-angiogenic agents are small molecules originated from natural sources. Recently, angiosuppressive effects of indirubin and its derivatives, the active components i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.12.003
更新日期:2012-03-01 00:00:00
abstract::Dimercaptosuccinic acid (DMSA) was shown to lower blood pressure in rat models of arterial hypertension. Thus, there is evidence that-besides its chelating properties-DMSA has a direct vascular effect, e.g. through scavenging of reactive oxygen species (ROS). We speculated that, in addition, intracellular calcium mobi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00121-7
更新日期:2003-05-15 00:00:00
abstract::Chronic exposure to the divalent heavy metals, such as iron, lead, manganese (Mn), and chromium, has been linked to the development of severe, often irreversible neurological disorders and increased vulnerability to developing Parkinson's disease. Although the mechanisms by which these metals elicit or facilitate neur...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0006-2952(03)00145-x
更新日期:2003-07-01 00:00:00
abstract::The effects of two competitive antagonists and two allosteric ligands on the rate of dissociation of [3H]N-methylscopolamine ([3H]NMS) were studied at atrial muscarinic acetylcholine M2 receptors by the technique of "infinite dilution." The dissociation rate for [3H]NMS, initiated by diluting the incubation mixture in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00814-3
更新日期:1997-03-21 00:00:00
abstract::Several drug compounds have failed in clinical trials due to extensive biotransformation by aldehyde oxidase (AOX) (EC 1.2.3.1). One of the main reasons is the difficulty in scaling clearance for drugs metabolised by AOX, from preclinical species to human. Using methotrexate as a probe substrate, we evaluated AOX meta...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.05.010
更新日期:2015-08-01 00:00:00
abstract::We examined the effects of amiloride derivatives, especially 5-(N-ethyl-N-isopropyl)amiloride (EIPA), on the activity of cytochrome P450 (CYP) 1 isoforms, known to metabolize carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BP), into mutagenic metabolites and whose cellular expression can ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.01.005
更新日期:2004-05-01 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::In this study we examined the metabolism of hypoxanthine in fibroblast growth factor (FGF)-stimulated porcine aortic endothelial cells (PAEC). Our previous report indicated that hypoxanthine in fetal bovine serum (FBS) was an essential component for both basal and FGF-dependent growth of PAEC (Hayashi et al., Exp Cell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90311-j
更新日期:1993-04-22 00:00:00
abstract::Protein kinase D (PKD) is a subfamily of serine/threonine specific family of kinases, comprised of PKD1, PKD2 and PKD3 (PKCμ, PKD2 and PKCv in humans). It is known that PKCs activate PKD, but the relative expression of isoforms of PKD or the specific PKC isoform/s responsible for its activation in platelets is not kno...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.06.032
更新日期:2011-10-01 00:00:00
abstract::Taxol-based chemotherapy is widely used as the first-line treatment for non-small cell lung cancer (NSCLC), however, the subsequent development of taxol-resistance is a major concern and challenge, resulting in tumor relapse and poor prognosis. Given the complex nature of taxol-resistance, we further delved into its m...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2019.113733
更新日期:2020-01-01 00:00:00
abstract::The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.09.015
更新日期:2016-12-01 00:00:00
abstract::The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90557-1
更新日期:1989-08-15 00:00:00
abstract::Multivalent dendrimeric conjugates of GPCR ligands may have increased potency or selectivity in comparison to monomeric ligands, a phenomenon that was tested in a model of cytoprotection in mouse HL-1 cardiomyocytes. Quantitative RT-PCR indicated high expression levels of endogenous A(1) and A(2A) adenosine receptors ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.03.020
更新日期:2010-07-15 00:00:00
abstract::The International Diabetes Federation predicts that by 2045 the number of individuals afflicted with diabetes will increase to 629 million. Furthermore, ∼352 million individuals with impaired glucose tolerance are at increased risk for developing diabetes. Several mechanisms have been proposed for the onset of metabol...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2018.04.026
更新日期:2018-08-01 00:00:00
abstract::In a previous study, we demonstrated that the serum of rats treated chronically with the anticancer agent Adriamycin contains lipid peroxides associated with neutral lipids (W. S. Thayer, Biochem Pharmacol 33: 2259-2263, 1984). In the present study, hearts from untreated control rats were perfused with medium containi...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90490-5
更新日期:1989-06-15 00:00:00