Abstract：
:Our previous study showed that organobismuth compounds induce apoptosis in human promyelocytic leukemia cells, although solid tumor cell lines were relatively resistant. Herein, we investigated the primary cellular target of these compounds in HeLa cells. One organobismuth compound, bi-chlorodibenzo[c,f][1,5]thiabismocine (compound 3), arrested the cell cycle at G(2)/M as assessed by flow cytometry and by upregulating the expression of cyclin B1. At a low concentration (0.5 microM), compound 3 caused cell cycle arrest at the mitotic phase and induced apoptosis. At a higher concentration (>1.0 microM), it induced an arrest in the G(2)/M phase, leading to apoptosis. In many cells blocked at the M phase, the organization of microtubules was affected, indicating depolymerization of the microtubule network. Western blotting demonstrated that compound 3 depolymerized microtubules similar to colchicine and nocodazole. Experiments in vitro also showed that compound 3 inhibited the assembly of purified tubulin in a concentration-dependent manner by interacting with the colchicine-binding site of tubulin through its SH groups. Heterocyclic organobismuth compounds are novel tubulin ligands.
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Iuchi K,Akagi K,Yagura Tdoi
10.1254/jphs.09020fpsubject
Has Abstractpub_date
2009-04-01 00:00:00pages
573-82issue
4eissn
1347-8613issn
1347-8648pii
JST.JSTAGE/jphs/09020FPjournal_volume
109pub_type
杂志文章abstract：:Cofilin, an actin-binding protein, is essential for a variety of cell responses. In this study, we investigated the correlation between proliferation and cofilin phosphorylation in response to platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMCs). The phosphorylation of cofilin and activity ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0072354
更新日期：2008-11-01 00:00:00
abstract：:Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR a...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2018.11.004
更新日期：2019-01-01 00:00:00
abstract：:Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliab...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2020.10.006
更新日期：2021-01-01 00:00:00
abstract：:Although mannitol has been used as an osmotherapeutic drug on brain injury, the clinical efficiency of the drug are still controversial. In the present study, we examined the effects of mannitol on the edema in a hippocampal slice due to brief ischemia. To evaluate the effects, we employed an image analysis system tha...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0030565
更新日期：2004-07-01 00:00:00
abstract：:We investigated the roles of β- and α(2)-adrenoceptors within the central nucleus of the amygdala (CeA) in the negative affective and sensory components of visceral pain in rats. We observed a dose-dependent reduction of intraperitoneal acetic acid-induced conditioned place aversion by bilateral injections of timolol,...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.10139sc
更新日期：2010-01-01 00:00:00
abstract：:Circulating endothelial progenitor cells (EPCs) derived from bone marrow were isolated for the first time in 1997 and characterized. Recent evidence has indicated that EPCs contribute to re-endothelialization of injured vessels as well as neovascularization of ischemic lesions and that a decrease in the number of EPCs...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.08r01cp
更新日期：2008-09-01 00:00:00
abstract：:The aim of this study was to classify antiarrhythmic drugs based on their effectiveness on 6 in vivo arrhythmia models, mainly using dogs. The models were produced by two-stage coronary ligation, digitalis, halothane-adrenaline, programmed electrical stimulation in old myocardial infarction dogs, coronary artery occlu...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.crj06013x
更新日期：2007-04-01 00:00:00
abstract：:Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in h...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2015.01.003
更新日期：2015-02-01 00:00:00
abstract：:In the present study, the characteristics of the sleep features of amitriptyline, mexiletine, and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyradine-1(2H)-carbox-amide (BCTC) were studied. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscles of rats for electroen...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.08059fp
更新日期：2008-07-01 00:00:00
abstract：:Overexpression of constitutively active (CA)-G alpha13 significantly increased the expression of interleukin (IL)-1beta and IL-6 mRNAs and proteins in rat cardiac fibroblasts. IL-1beta mRNA induction by CA-G alpha13 was suppressed by diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, but not by BAPTA-AM, an intrac...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0051036
更新日期：2006-06-01 00:00:00
abstract：:The critical role played by the renin-angiotensin-aldosterone system (RAAS) in the regulation of blood pressure and body fluid homeostasis has been well recognized. Angiotensin (Ang) II and aldosterone are the most powerful biologically active products of the RAAS, although there are also other bioactive Ang peptides ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.10r03fm
更新日期：2010-01-01 00:00:00
abstract：:In this study, we clarified the intracellular mechanism of angiotensin II (Ang II) in promoting migration in rat aortic smooth muscle cells (RASMCs). RASMC migration was measured with the Boyden chamber assay, and the result was confirmed with an aortic sprout assay. The activities of kinases were investigated by west...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0070770
更新日期：2007-09-01 00:00:00
abstract：:Photodynamic therapy (PDT) is an evolving cancer treatment with promising results in treating malignant tumors by photoactivation of a photosensitizer with a specific wavelength. The second generation photosensitizer mono-L-aspartyl chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer cells in...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.93.136
更新日期：2003-10-01 00:00:00
abstract：:Neurite outgrowth is a complex differentiation process regulated by external and/or internal mechanisms. Among external mechanisms, G-protein coupled receptors (GPCRs) have been implicated in this process, but the pathways involved are not fully understood. L-3,4-dihydroxyphenylalanine (l-DOPA) is considered to be ine...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.09.002
更新日期：2019-09-01 00:00:00
abstract：:Opioid analgesics are widely used for the treatment of moderate to severe pain. The analgesic effects of opioids are well known to vary among individuals. The present study focused on the genetic factors that are associated with interindividual differences in pain and opioid sensitivity. We conducted a multistage geno...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2018.02.002
更新日期：2018-03-01 00:00:00
abstract：:Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. Here we report the effects of neurosteroids on the function of Na(v), using voltage-clamp techniques in Xenopus oocytes expressed ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.12106sc
更新日期：2012-01-01 00:00:00
abstract：:Intravital multiphoton microscopy has opened a new era in the field of biological imaging. Focal excitation of fluorophores by simultaneous attack of multiple (normally "two") photons generates images with high spatial resolution, and use of near-infrared lasers for multiphoton excitation allows penetration of thicker...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.12r03cp
更新日期：2012-01-01 00:00:00
abstract：:Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug that can potentiate some acute allergies and causes adverse immunological reactions collectively referred to as aspirin intolerance, a disorder that induces urticaria, asthma, and anaphylaxis in response to oral administration of the dr...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.08r32fm
更新日期：2009-07-01 00:00:00
abstract：:We have demonstrated previously that the ketamine-induced discriminative stimulus effect is likely to reflect the phencyclidine-like psychotomimetic effects. Therefore, the present study was designed to investigate the effects of the antipsychotics and 5-HT2 receptor antagonist on the discriminative stimulus effects o...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.12148sc
更新日期：2013-01-01 00:00:00
abstract：:The role of extracellular calcium in the interaction between intracellular cAMP and nitric oxide (NO)/cGMP on the contractility of rat diaphragm pretreated with cumulative concentrations of aminophylline (0.36 - 3.60 mM) was investigated. In a Ca2+-free medium, NG-nitro-L-arginine methyl ester (L-NAME) (1 and 3 mM) de...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.sce04001x
更新日期：2004-12-01 00:00:00
abstract：:Melittin is a major peptide component of sweet bee venom that possesses anti-allergic, anti-inflammatory, anti-arthritis, anti-cancer, and neuroprotective properties. However, the therapeutic effects of melittin on muscle injury have not been elucidated. We investigated the therapeutic effects of melittin on muscle in...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.03.009
更新日期：2019-05-01 00:00:00
abstract：:The purpose of the current study was to explore the effects of N-methyl-D-aspartate (NMDA)-receptor antagonists (MK-801 and LY235959) administered intracerebroventricularly on the changes of both core temperature and hypothalamic levels of 2,3-dihydroxybenzoic acid (2,3-DHBA) induced by intracerebroventricular injecti...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0070272
更新日期：2007-06-01 00:00:00
abstract：:Incomplete recovery of myocardial contraction after reperfusion following brief ischemia is called the "stunning phenomenon" in an animal experiment. A hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) does not affect this phenomenon, but lipophilic statins further reduce the con...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.08017fp
更新日期：2008-04-01 00:00:00
abstract：:The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder can...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2015.05.005
更新日期：2015-06-01 00:00:00
abstract：:We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an ele...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.09142fp
更新日期：2009-09-01 00:00:00
abstract：:Peripheral-type benzodiazepine receptor (PBR) and central-type benzodiazepine receptor (CBR) in salivary gland play a role in the inhibitory regulation of salivary secretion in rodents. Diazepam-binding inhibitor (DBI), an endogenous ligand for PBR, produces neurosteroids, which modulate CBR activity. In this study, w...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.10282FP
更新日期：2011-01-01 00:00:00
abstract：:The hippocampus is a brain region well-known to exhibit structural and functional changes in temporal lobe epilepsy. Studies analyzing the brains of patients with epilepsy and those from animal models of epilepsy have revealed that microglia are excessively activated, especially in the hippocampus. These findings sugg...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.jphs.2020.09.003
更新日期：2020-12-01 00:00:00
abstract：:A novel AMP-activated protein kinase (AMPK) activator, IMM-H007 (H007), has been reported to reduce serum lipid levels and inhibit lipid accumulation in the liver in hyperlipidemic animal models. However, how H007 ameliorates hepatic steatosis and inflammation remains unknown. In the present study, H007, at 200 mg/kg,...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.05.008
更新日期：2019-06-01 00:00:00
abstract：:We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0072051
更新日期：2008-02-01 00:00:00
abstract：:We aimed to examine the rate of thrombotic events after discontinuation of one year clopidogrel therapy in patients with implanted coronary stent, and to determine platelet aggregability by multiple electrode analyzer after cessation of clopidogrel. This prospective, multicenter study enrolled 200 patients subjected t...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.11076fp
更新日期：2011-01-01 00:00:00
