Abstract:
AIM:To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. METHODS:Cell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis. RESULTS:LGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production. CONCLUSION:The activity of LGH00031 at the molecular and cellular level is mediated by ROS.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Zhou YB,Feng X,Wang LN,Du JQ,Zhou YY,Yu HP,Zang Y,Li JY,Li Jdoi
10.1038/aps.2009.131subject
Has Abstractpub_date
2009-09-01 00:00:00pages
1359-68issue
9eissn
1671-4083issn
1745-7254pii
aps2009131journal_volume
30pub_type
杂志文章abstract:AIM:To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. METHODS:Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00828.x
更新日期:2008-08-01 00:00:00
abstract:AIM:To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). METHODS:The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newl...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:AIM:To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro. METHODS:A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylli...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,随机对照试验
doi:10.1038/aps.2011.78
更新日期:2011-10-01 00:00:00
abstract::Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exac...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00525-z
更新日期:2020-09-23 00:00:00
abstract:AIM:To explore correlation of T helper 1 (Th1) and Th2 cytokine between the cortical layer and pulmonary airway in ovalbumin-induced rat asthma model. METHODS:Aerosol antigen-induced changes of inflammation in bronchoalveolar lavage fluids (BALF) and pulmonary histologic section in sensitized rats were investigated. C...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract:AIM:To characterize the in vitro bioactivities of rhodanine derivatives as novel peroxisome proliferator-activated receptor (PPAR) gamma modulators, based on a hit (SH00012671) identified during high-throughput screening (HTS) of a diverse synthetic compound library, and to preliminarily elucidate the structure-activit...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract:AIM:To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model. METHODS:Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior descending...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00306.x
更新日期:2006-05-01 00:00:00
abstract::Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in thi...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00058.x
更新日期:2005-03-01 00:00:00
abstract:AIM:To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. METHODS:Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.158
更新日期:2013-02-01 00:00:00
abstract:AIM:To investigate the actions of the muscarinic agonist carbachol on glutamate-induced neurotoxicity in PC12 cells, and the underlying mechanisms. METHODS:PC12 cells were treated with different concentrations of glutamate for 24 or 48 h. The cell viability was measured using MTT assay, and the expression and activati...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.42
更新日期:2013-07-01 00:00:00
abstract::Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, E...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2014.123
更新日期:2015-01-01 00:00:00
abstract:AIM:Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 in...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.60
更新日期:2016-09-01 00:00:00
abstract::Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromoso...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00126.x
更新日期:2005-06-01 00:00:00
abstract:AIM:To find novel proteins that may bind to alpha1A-adrenergic receptor (alpha1A-AR) and investigate their interactions with the other two alpha1-AR subtypes (alpha1B-AR and alpha1D-AR) with an expectation to provide new leads for the function study of the receptors. METHODS:Yeast two-hybrid assay was performed to scr...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract:AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:AIM:To study the association between APOE polymorphisms and cerebral infarction through a case-control study among the Chinese Han population. METHODS:First-ever cerebral infarction patients (n=226) whose ages ranged from 40 to 60 years old were recruited from Department of Neurology, Zhongshan Hospital, Shanghai, and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:AIM:Targeting the VEGF/VEGF receptor (VEGFR) pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-((2-((3-acetamidophenyl)amino)pyrimidin-4-yl)oxy)-N-phenyl-1-naphthamide (designated herein as DW10075) as a novel and highly selective inhibitor of VEGFRs. METHODS:In ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.117
更新日期:2016-03-01 00:00:00
abstract::Recently, two different chemicals have been matched as ligands with the same G-protein-coupled receptor (GPCR). Double-pairing of OGR1 family GPCRs with proton and lysolipid raises several questions. First, whether both are the real ligands for the GPCRs. Second, whether modulation of a GPCR by two chemicals could be ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2005.00237.x
更新日期:2005-12-01 00:00:00
abstract:AIM:To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. METHODS:In 6 beagles, a basket ca...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.96
更新日期:2012-12-01 00:00:00
abstract:AIM:To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro. METHODS:Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Weste...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00550.x
更新日期:2007-07-01 00:00:00
abstract:AIM:To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS:Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were tre...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.133
更新日期:2014-01-01 00:00:00
abstract:AIM:The metabolites of naproxen produced by Cunninghamella species were isolated and identified, and further to compare the similarities between microbial transformation and mammalian metabolism. METHODS:Naproxen was transformed by three strains of Cunninghammella species (Cunninghamella blakeslesna AS 3.153, Cunningh...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::DJ-1 is a multifunctional protein associated with cancers and autosomal early-onset Parkinson disease. Besides the well-documented antioxidative stress activity, recent studies show that DJ-1 has deglycation enzymatic activity and anti-ferroptosis effect. It has been shown that DJ-1 forms the homodimerization, which d...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00531-1
更新日期:2020-10-06 00:00:00
abstract:AIM:To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C. METHODS:After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00474.x
更新日期:2007-02-01 00:00:00
abstract::Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure-activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 h...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0354-1
更新日期:2020-06-01 00:00:00
abstract:AIM:Apolipoprotein E (ApoE) plays an important role in the transport and metabolism of lipids. Recent studies show that bone mass is increased in young apoE(-/-) mice. In this study we investigated the bone phenotype and metabolism in aged apoE(-/-) mice. METHODS:Femurs and tibias were collected from 18- and 72-week-o...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.95
更新日期:2015-12-01 00:00:00
abstract:AIM:To study the effects of 3-n-butylphthalide (NBP) on the TREK-1 channel expressed in Chinese hamster ovary (CHO) cells. METHODS:Whole-cell patch-clamp recording was used to record TREK-1 channel currents. The effects of varying doses of l-NBP on TREK-1 currents were also observed. Current-clamp recordings were perf...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.210
更新日期:2011-02-01 00:00:00
abstract:AIM:To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. METHODS:Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 μmol/L) for various lengths of time. For pharmacological experiments,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.59
更新日期:2012-07-01 00:00:00
abstract:AIM:alpha2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of alpha2* nAChRs in these mouse brain regions. METHODS:alpha2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.68
更新日期:2009-06-01 00:00:00
abstract:AIM:Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent in green tea. The aim of this study is to investigate the effects of EGCG on proliferation and migration of the human colon cancer SW620 cells. METHODS:Proliferation and migration of SW620 cells were induced by the protease-activated receptor ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.139
更新日期:2012-01-01 00:00:00