Abstract:
:Metformin is an antidiabetic drug recently shown to inhibit cancer cell proliferation and growth, although the involved molecular mechanisms have not been elucidated. In many cancer cells, high expression of thymidine phosphorylase (TP) and Excision repair cross-complementation 1 (ERCC1) is associated with poor prognosis. We used A549 and H1975 human non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity. Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner. The enforced expression of the constitutively active MEK1 (MEK1-CA) vectors significantly restored cellular TP and ERCC1 protein levels and cell viability. Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition. Arachidin-1, an antioxidant stilbenoid, further decreased TP and ERCC1 expression and augmented metformin's cytotoxic effect, which was abrogated in lung cancer cells transfected with MEK1/2-CA expression vector. In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells.
journal_name
Basic Clin Pharmacol Toxicoljournal_title
Basic & clinical pharmacology & toxicologyauthors
Ko JC,Huang YC,Chen HJ,Tseng SC,Chiu HC,Wo TY,Huang YJ,Weng SH,Chiou RY,Lin YWdoi
10.1111/bcpt.12052subject
Has Abstractpub_date
2013-07-01 00:00:00pages
56-65issue
1eissn
1742-7835issn
1742-7843journal_volume
113pub_type
杂志文章abstract::Copper deficiency had been suggested to link between fructose-enriched diet (FED) and the development of non-alcoholic fatty liver disease (NAFLD). In this study, we characterized changes in hepatic copper concentrations and hepatic oxidative milieu, in rats with the metabolic syndrome and NAFLD as a result of FED wit...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12283
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abstract::Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disease with high mortality. Dithiocarbamates (DTC) are organosulphur compounds widely used in agriculture, industry and households. We report a case of TEN after exposure to mancozeb in fungicide. A 48-year-old 75 kg b.w. man was admitted with fever...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12430
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abstract::Extracts of six commonly used commercially available herbal products, St. John's wort, common valerian, common sage, Ginkgo biloba, Echinacea purpurea and horse chestnut were investigated for their in vitro inhibitory potential of CYP3A4 mediated metabolism and P-glycoprotein efflux transport activity. C-DNA baculovir...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2008.00227.x
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abstract::The essential oil of Alpinia zerumbet (EOAz) presents myorelaxant and antispasmodic actions on cardiac and smooth muscles. The aim of this study was to investigate the effect of EOAz on the skeletal muscle contraction in post-stroke spasticity. Fifteen adults with unilateral hemiparesis and spasticity resulting from s...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 临床试验,杂志文章
doi:10.1111/bcpt.12439
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abstract::This study was designed to investigate the therapeutic effect of sodium formononetin-3'-sulphonate (Sul-F), a water-soluble derivate of formononetin, on acute myocardial infarction in rats. The results showed that treatment with Sul-F significantly prevented the elevation of ST-segment level, decreased the contents of...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2011.00676.x
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abstract::The era of immunotherapies was unleashed in 2010 with the Food and Drug Administration (FDA) approval of the first therapeutic vaccine sipuleucel-T as a standard treatment for metastatic prostate cancer. Next, the first immune-activating anticytotoxic lymphocyte antigen-4 (CTLA-4) antibody ipilimumab exhibiting 'immun...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
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abstract::The use of herbal or natural medicines for the treatment of various disorders has a long and extensive history. Many of these herbal medicines are finding their way onto the world market as alternatives to prescribed drugs currently available to treat various disorders/ailments. In particular, hyperlipidaemia is a maj...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
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更新日期:2005-01-01 00:00:00
abstract::Although atracurium is a widely used neuromuscular blocker, we still lack knowledge regarding some of its cellular mechanisms of action. Thus, similar to other clinically used blockers atracurium induces, both in vivo and in vitro, fade of the tetanic contraction. However, the cellular mechanisms underlying this tetan...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2004.pto950103.x
更新日期:2004-07-01 00:00:00
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journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2006.pto_343.x
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journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2005.pto_973123.x
更新日期:2005-09-01 00:00:00
abstract::To study the influence of single or repeated low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to low clinically asymptomatic concentrations of sarin for 60 min. in the inhalation chamber. The evaluation of immune functions was carried out using phenotyping of CD3 (T-lymphocytes)...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2004.pto940307.x
更新日期:2004-03-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (sEVs) are promising candidates for cell-based and cell-free regenerative medicine, respectively. By virtue of their multiple lineage differentiation capacity, MSCs have been implicated as an ideal tool for bone and cartilage regeneration. Howe...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13478
更新日期:2021-01-01 00:00:00
abstract::Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an i...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12743
更新日期:2017-06-01 00:00:00
abstract::To study the potential interactions of naringin (NAR), talinolol (TAL) and protein-energy undernutrition (PEU) in the absorption process of saquinavir (SQV), perfusion experiments were performed in the small intestine of rats at different SQV concentrations. The results obtained demonstrated that SQV intestinal absorp...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2011.00714.x
更新日期:2011-10-01 00:00:00
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journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12854
更新日期:2018-01-01 00:00:00
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journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/j.1742-7843.2007.00149.x
更新日期:2008-01-01 00:00:00
abstract::Alzheimer's disease is a neurodegenerative disorder that is characterized by the accumulation of senile plaques containing amyloid β (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein in the brain. Oxidative stress has been proposed to mediate Aβ-induced neurotoxicity. In that regard, we eval...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00664.x
更新日期:2011-06-01 00:00:00
abstract::Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6-thioguanine nucleotides (6-TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as fo...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13176
更新日期:2019-05-01 00:00:00
abstract::Fluorochemicals are a diverse group of synthetically produced compounds with the unique ability to repel water as well as oil. This property makes them ideal for multiple purposes in a variety of consumer and industrial products. Fluorochemicals have been detected in the environment, as well as in human blood, urine a...
journal_title:Basic & clinical pharmacology & toxicology
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doi:10.1111/bcpt.12208
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abstract::Clozapine and caffeine are metabolised mainly by the cytochrome P4501A2 (CYP1A2) enzyme. Studies suggest that caffeine in coffee inhibits clozapine metabolism and increases serum clozapine concentrations. Our objective was to study whether coffee in the amounts usually consumed has an effect on steady-state serum cloz...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2004-01-01 00:00:00
abstract::To investigate the transplacental transport of pesticides, the pyrethroid cypermethrin and the fungicide azoles, propiconazole and bitertanol were tested in the placental perfusion model. Cypermethrin, propiconazole and bitertanol were also tested in the BeWo cell transfer model. The pesticides were chosen with the se...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.13456
更新日期:2020-12-01 00:00:00
abstract::The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00653.x
更新日期:2011-05-01 00:00:00
abstract::Natural oils are extensively used in cosmetics and as treatment for a growing number of more or less specific ailments. Skin irritation and cases of allergy have repeatedly been described in the literature following exposure to these oils. The present study evaluated the extent to which three natural oils (eucalyptus ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2006.pto_388.x
更新日期:2006-06-01 00:00:00
abstract::Despite increased awareness and intensified biomedical research efforts, the prevalence of obesity continues to rise worldwide. This is alarming, because obesity accelerates the progression of several chronic disorders, including type 2 diabetes, cancer and cardiovascular disease. Individuals who experience significan...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
doi:10.1111/bcpt.13311
更新日期:2020-06-01 00:00:00
abstract::Most steroid hormones are produced from cholesterol contained in low-density lipoproteins, which is uptaken by the gonads and adrenal cortex, and used as a substrate for steroidogenesis. Theoretically, in states associated with very low-density lipoprotein (LDL) cholesterol levels, cholesterol conversion to steroid ho...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12169
更新日期:2014-04-01 00:00:00
abstract::Maximizing the likelihood of success in Phase III is the ultimate goal of the use of modelling and simulation in the drug development process. The success in Phase III depends primarily on two questions: 1) Is the drug regimen actually efficacious and safe in the targeted patient population?, and 2) Will the planned P...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2005.pto960314.x
更新日期:2005-03-01 00:00:00
abstract::Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00561.x
更新日期:2010-09-01 00:00:00
abstract::The constitutive endothelial nitric oxide synthase (eNOS) plays a major role in circulatory homoeostasis and shows genetic polymorphism. eNOS is expressed and functional in blood cells, including erythrocytes. There is limited knowledge about the consequences of eNOS genetic variability in haemorheological parameters ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/j.1742-7843.2010.00637.x
更新日期:2011-03-01 00:00:00
abstract::The potent neurotoxin saxitoxin (STX) belongs to a group of structurally related analogues produced by both marine and freshwater phytoplankton. The toxins act by blocking voltage-gated sodium channels stopping the inflow of sodium ions and the generation of action potentials. Exposure from marine sources occurs as a ...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章
doi:10.1111/bcpt.12701
更新日期:2017-04-01 00:00:00
abstract::Curcumin is the effective ingredient of turmeric, sometimes used as a painkiller in traditional medicine. It has extensive biological properties such as anti-inflammatory and antioxidant activities. SARS-CoV-2 is a betacoronavirus developing severe pneumonitis. Inflammasome is one of the most important components of i...
journal_title:Basic & clinical pharmacology & toxicology
pub_type: 杂志文章,评审
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更新日期:2021-01-01 00:00:00