Abstract：
:We investigated the amplification of bleomycin-induced DNA cleavage by synthetic triamides containing N-methylpyrrole (Py) and/or N-methylimidazole (Im), PyPyPy, PyPyIm, PyImPy, and PyImIm, using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 and p53 genes. Peplomycin, a bleomycin analog, plus Fe(II) caused DNA cleavage at the 5'-GC-3' and 5'-GT-3' sequences (damaged bases are underlined). The addition of PyPyPy dramatically enhanced the cleavage, particularly at cytosine residues 3' to consecutive guanines. Alteration in the site specificity was not observed with other triamides (PyPyIm, PyImPy, and PyImIm). DNase I footprinting revealed that PyPyPy bound to the sites adjacent to the sites where DNA cleavage was enhanced by PyPyPy, and that PyPyPy enhanced DNase I-induced cleavage in GC-rich regions. These findings suggest that binding of PyPyPy to the DNA minor groove changes the DNA conformation to allow peplomycin to cleave DNA more efficiently at GC-rich sequences, resulting in intensive site-specific DNA cleavage particularly at cytosines at the 3'-side of polyguanines. The present study on amplifiers of antitumor drugs would appear to offer a novel approach to the establishment of more effective chemotherapy.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Hiraku Y,Oikawa S,Kuroki K,Sugiyama H,Saito I,Kawanishi Sdoi
10.1016/s0006-2952(00)00563-3subject
Has Abstractpub_date
2001-02-01 00:00:00pages
351-6issue
3eissn
0006-2952issn
1873-2968pii
S0006-2952(00)00563-3journal_volume
61pub_type
杂志文章abstract：:The influence of monoamine oxidases A and B on the metabolism of dopamine or the expanded dopamine pool following L-dopa administration remains unclear. This study found that treatment of Sprague-Dawley rats with monoamine oxidase inhibitors strongly affected L-dopa metabolism in the brain, but the influence varied wi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90060-8
更新日期：1987-05-15 00:00:00
abstract：:The participation of mitochondria in the mechanism of tumor cell death induced by non-steroid anti-inflammatory drugs is uncertain. Here we show that ibuprofen induces death of Walker 256 tumor cells independently on mitochondrial depolarization as estimated by flow cytometry using DioC(6)(3). Oligomycin increased mit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.08.006
更新日期：2004-12-01 00:00:00
abstract：:The development of the plasma cell tumor (PCT) model was the first widely accepted in vivo model of multiple myeloma (MM). Potter and colleagues used this chemically induced PCT model to study the pathophysiology of malignant plasma cells and also used it to screen anti-MM agents. Two decades later the C57BL/KaLwRij m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.03.013
更新日期：2014-06-01 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：: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
更新日期：2003-08-15 00:00:00
abstract：:Cyclophosphamides are pro-drugs whose killing agent is produced from an aldehyde that is formed by the action of a P450 oxidation step. The mustard from the aldehyde can destroy bone marrow cells as well as the tumor. Aldehyde dehydrogenase (EC 1.2.1.3) can oxidize the aldehyde and hence inactivate the cytotoxic inter...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.06.018
更新日期：2008-09-01 00:00:00
abstract：:Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.09.022
更新日期：2016-12-15 00:00:00
abstract：:Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90016-x
更新日期：1991-01-01 00:00:00
abstract：:Here we report on the induction of resistance to photodynamic therapy (PDT) in the ABCG2-high human breast cancer cell line MA11 after repetitive PDT, using either Pheophorbide A (PhA) or di-sulphonated meso-tetraphenylchlorin (TPCS2a) as photosensitizer. Resistance to PhA-PDT was associated with enhanced expression o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.08.002
更新日期：2017-11-15 00:00:00
abstract：:The antimalarial artemisinin derivatives artesunate (ART), arteether (ARE), and artemether (ARM) reveal remarkable antineoplastic activity. In the present investigation, we identified mRNA expression profiles associated with the response of tumor cells to ART, ARE, and ARM. We performed correlation and hierarchical cl...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01221-2
更新日期：2002-08-15 00:00:00
abstract：:The characteristics of the muscarinic receptor in isolated gastric fundic cells from rabbit were determined by radioligand binding techniques and functional tests. The dissociation constants (KDS) of selective (hexahydrosiladifenidol and pirenzepine) and non-selective (N-methylscopolamine and atropine) muscarinic rece...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90209-7
更新日期：1987-09-15 00:00:00
abstract：:Enhanced DNA repair activity is important for the development of cellular resistance to alkylating agents. Here, we quantitated the kinetics of DNA excision repairs initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells. CEM cells that had been established resistant to BCNU (CEM-R) w...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00412-x
更新日期：2003-09-15 00:00:00
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
更新日期：1998-07-01 00:00:00
abstract：:High concentrations of non steroidal antiinflammatory drugs (NSAIDs) exert preventive effects against carcinogenesis. Their molecular mechanism of action remains to be elucidated. Based on previous reports with salicylate, we have made the hypothesis that various NSAIDs can activate the mitogen-activated protein kinas...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00826-7
更新日期：2002-01-15 00:00:00
abstract：:Growing evidence suggests that hepatic-insulin resistance is sufficient to promote progression to cardiovascular disease. We have shown previously that liver-specific protein-tyrosine-phosphatase 1B (PTP1B) deficiency improves hepatic-insulin sensitivity and whole-body glucose homeostasis. The aim of this study was to...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.10.008
更新日期：2014-12-15 00:00:00
abstract：:The family of natural red pigments, called prodigiosins (PGs), characterised by a common pyrrolylpyrromethene skeleton, are produced by various bacteria. Some members have immunosuppressive properties and apoptotic effects in vitro and they have also displayed antitumour activity in vivo. Understanding the mechanism o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(03)00496-9
更新日期：2003-10-15 00:00:00
abstract：:The inhibition of renal ornithine decarboxylase (ODC) by aminoglycoside antibiotics was characterized in the postmitochondrial fraction of a kidney homogenate from adult pigmented guinea pigs. Enzymatic activity was defined as the rate of decarboxylation of [14C]ornithine sensitive to a specific ODC inhibitor, alpha-d...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90427-3
更新日期：1988-05-01 00:00:00
abstract：:Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90529-4
更新日期：1983-02-01 00:00:00
abstract：:A large variety of 5-substituted 2'deoxyuridines (dUrds) and 2'-deoxyuridylates (dUMPs) have been evaluated for their inhibitory effects on the thymidine (dThd) kinase or thymidylate (dTMP) synthetase isolated from mouse leukemia L1210 cells. The most potent inhibitors of dThd kinase were 5-chloro-, 5-bromo- and 5-iod...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90594-9
更新日期：1982-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.113670
更新日期：2020-01-01 00:00:00
abstract：:This mini-review addresses the effect of glycosylation and phosphorylation on the conformational alterations of the epidermal growth factor receptor (EGFR). Based on studies with full-length and truncated EGFRs, we propose a model to suggest that receptor-receptor self-association, which occurs in the truncated recept...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(00)00425-1
更新日期：2000-10-15 00:00:00
abstract：:Sublines of K562 human leukemia cells were selected for resistance (30- to 80-fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide-resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of topoisomerase II alpha protein compared with K562 cells. Northern analysis indicat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90643-b
更新日期：1993-12-03 00:00:00
abstract：:It was previously shown that [Pt(O,O'-acac)(γ-acac)(DMS)] induces apoptosis in various cancer cells and exerts antimetastatic responses in vitro. In rats, [Pt(O,O'-acac)(γ-acac)(DMS)] reaches the central nervous system in quantities higher than cisplatin causing less excitotoxicity. The aim of the present paper was to...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.03.007
更新日期：2011-06-01 00:00:00
abstract：:The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.06.018
更新日期：2011-10-15 00:00:00
abstract：:Anti-idiotypic antibodies which recognize the opiate receptor were generated in guinea pigs following immunization against purified rabbit anti-morphine antibodies. The anti-idiotypic antibodies produced a concentration-dependent inhibition of [3H]naloxone binding to opiate receptors in a membranous mouse brain prepar...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90006-1
更新日期：1985-08-15 00:00:00
abstract：:Perfluorodecanoic acid (PFDA) alters the circulating level of thyroid hormones, but the physiological significance of this change at the target tissue remains to be defined. To this end, the activities of thyroid-responsive hepatic enzymes were examined in adult male rats 1 week after treatment with a single dose of P...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90091-8
更新日期：1987-04-15 00:00:00
abstract：:The immunosuppressive and cytostatic agent 15-deoxyspergualin (DSG) binds to the Hsc70 class of molecular chaperones with a K(D) = 4 microM. Because Hsc70s represent a diverse group of cellular effectors and because Hsc70 function frequently requires a DnaJ molecular chaperone, the specificity of DSG for different Hsc...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00376-1
更新日期：1999-04-15 00:00:00
abstract：:Enhanced aggregation of platelets was observed in platelet-rich plasma, but not in washed platelet suspension (WPS), during acute inflammation in rats. Incubation of WPS with inflammatory plasma increased the aggregatory response to ADP, but the plasma itself did not cause aggregation of platelets. It potentiated the ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90699-l
更新日期：1990-07-15 00:00:00
abstract：:The expression of xenobiotic-metabolising cytochrome P450 proteins in the liver of cattle was determined using substrate probes and immunologically by Western blot analysis. Compared to the rat, cattle displayed much higher coumarin 7-hydroxylase (CYP2A) and ethoxyresorufin O-deethylase (CYP1) activity but, in contras...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00710-9
更新日期：2001-09-01 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
