Abstract：
:Anoikis is defined as apoptosis, which is induced by inappropriate cell-matrix interactions. Cancer cells with anoikis resistance tend to undergo metastasis, and this phenomenon has been reported to be associated with integrin and FAK activity. HPW-RX40 is a derivative of 3,4-methylenedioxy-β-nitrostyrene, which is known to prevent platelet aggregation by inhibition of integrin. In the present study, we investigated the effect of HPW-RX40 on an anoikis-resistant human breast cancer cell line MDA-MB-231. HPW-RX40 inhibited cell aggregation and induced cell death in suspending MDA-MB-231 cells, but had only little effect on the monolayer growth of adherent cells. Analysis of caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage confirmed anoikis in HPW-RX40-treated suspending cancer cells. HPW-RX40 also affected the Bcl-2 family proteins in detached cancer cells. Furthermore, HPW-RX40 inhibited detachment-induced activation of FAK and the downstream phosphorylation of Src and paxillin, but did not affect this pathway in adherent cancer cells. We also found that the expression and activation of β1 integrin in MDA-MB-231 cells were reduced by HPW-RX40. The combination of HPW-RX40 with an EGFR inhibitor led to enhanced anoikis and inhibition of the FAK pathway in breast cancer cells. Taken together, our results suggest that HPW-RX40 restores the anoikis sensitivity in the metastatic breast cancer cells by inhibiting integrin and subsequent FAK activation, and reveal a potential strategy for prevention of tumor metastasis.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Chen IH,Shih HC,Hsieh PW,Chang FR,Wu YC,Wu CCdoi
10.1016/j.taap.2015.09.011subject
Has Abstractpub_date
2015-12-01 00:00:00pages
330-40issue
2eissn
0041-008Xissn
1096-0333pii
S0041-008X(15)30085-5journal_volume
289pub_type
杂志文章abstract：:Immobilization of nanoparticles on inorganic supports has been recently developed, resulting in the creation of nanocomposites. Concerning titanium dioxide nanoparticles (TiO2 NPs1), these have already been developed in conjugation with clays, but so far there are no available toxicological studies on these nanocompos...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2016.12.018
更新日期：2017-02-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environmental pollutant and is well known for inducing thymic atrophy in mice, although the exact mechanism of its action remains unclear. Recent studies from our laboratory demonstrated that TCDD induces apoptosis in thymocytes and that Fas- mice (lpr/lpr) ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8390
更新日期：1998-05-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD),12 the most toxic congener of dioxins, exhibits wide sensitivity differences between a sensitive Long-Evans (L-E) rat and a resistant Han/Wistar (H/W) rat. The sensitivity is determined probably by two autosomal genes and it is highly end point dependent. The difference is mo...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1998.8564
更新日期：1999-02-15 00:00:00
abstract：:(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact mol...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2020.115100
更新日期：2020-08-15 00:00:00
abstract：:Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens an...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.05.021
更新日期：2009-09-15 00:00:00
abstract：:Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation a...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.03.022
更新日期：2017-06-01 00:00:00
abstract：:The purpose of this study was to characterize the induction of metallothionein (MT) by steroids in rat primary hepatocyte cultures. Comparison of the characteristics of MT induction by a steroid (dexamethasone) to that by metals (Zn and Cd), examination of the involvement of the glucocorticoid receptor in the steroid ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90242-0
更新日期：1987-03-15 00:00:00
abstract：:Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the tre...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2005.07.004
更新日期：2006-04-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.03.008
更新日期：2012-05-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90025-p
更新日期：1990-02-01 00:00:00
abstract：:A group of alkyl epoxides was compared for their guinea pig sensitization capacity and reactivities towards a protein-surrogate substrate, n-butylamine. Instead of the previously reported use of a titration method for determination of alkylation rate, proton nuclear magnetic resonance spectrometry (1H NMR) was used. T...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(91)90094-u
更新日期：1991-05-01 00:00:00
abstract：:The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was investigated in rainbow trout (Oncorhynchus mykiss) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in rainbow trout compared to other species. The fish were dosed ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0183
更新日期：1996-08-01 00:00:00
abstract：:Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was in...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2017.01.013
更新日期：2017-03-01 00:00:00
abstract：:Ammonium perfluorooctanoate (CAS Registry No. 3825-26-2) is used commercially in the aqueous polymerization of fluorinated monomers. Because the chemical exists as a fine white powder which can come in contact with skin, its dermal toxicology was studied in rabbits and rats. Dermal applications of 0.5 g for 24 hr prod...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90172-3
更新日期：1985-11-01 00:00:00
abstract：:Organic chemicals such as jet fuels and solvents can cause skin irritation after dermal exposure. The molecular responses to these chemicals resulting in acute irritation are not understood well enough to establish safe exposure limits. Male F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top Cham...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2001.9248
更新日期：2001-08-15 00:00:00
abstract：:To determine if inhaled nephrotoxic branched and nonnephrotoxic straight chain alkanes differ substantially in their biological fate, male F344 rats were exposed to 14C-labeled isooctane and octane vapors at approximately 1 and 350 ppm by the nose-only mode for 2 hr. Radioactivity in exhalant, urine, and feces was det...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90319-0
更新日期：1989-09-01 00:00:00
abstract：:Historical studies report that cellular injury and silicosis are related to cytosolic free calcium (Ca2+). Moreover, reactive oxygen species (ROS) have been linked to cellular injury. However, the detail mechanism of the increase in [Ca2+]i and the relationship between [Ca2+]i and ROS production remains unknown. Quart...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.10.005
更新日期：2010-01-15 00:00:00
abstract：:Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin f...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(89)90272-x
更新日期：1989-11-01 00:00:00
abstract：:Cadmium/Hg interactions have been studied in the TC7 clone of the enterocytic-like Caco-2 cells to test the hypothesis that these metals may compete for intestinal transport. Comparison of the kinetic parameter values for 203Hg(II) and 109Cd(II) uptake in a serum-free medium revealed that Hg is accumulated much more r...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00085-1
更新日期：2003-05-15 00:00:00
abstract：:p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelia...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90372-y
更新日期：1992-07-01 00:00:00
abstract：:Fumonisins are carcinogenic to rats and are suspected human carcinogens. However, the mechanism(s) of carcinogenesis of fumonisn B1 (FB1) is poorly understood. Multiple signal transduction pathways such as protein kinase C (PKC) have been shown to play an important role in carcinogenesis. This study was undertaken to ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1996.0274
更新日期：1996-11-01 00:00:00
abstract：:To evaluate the functional significance of bis(tri-n-butyltin)oxide (TBTO)-induced thymus atrophy, lymphocyte depletion in spleen and lymph nodes, lymphopenia, and increased serum IgM and decreased IgG concentrations, in vivo and in vitro function studies were performed for specific and nonspecific resistance. Weaned ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90177-7
更新日期：1984-09-30 00:00:00
abstract：:Interleukin-6 (IL-6) is a central mediator of immunotoxicity that is associated with exposure to the trichothecene vomitoxin (VT). The purpose of this investigation was to test the hypothesis that the inducible cyclooxygenase-2 (COX-2) and its metabolites contribute to VT-induced IL-6 upregulation. VT at 100 to 250 ng...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(02)00033-9
更新日期：2003-03-01 00:00:00
abstract：:The effect of age and sex on the elimination of theophylline in New Zealand White rabbits was investigated following exposure to 0.3 ppm of ozone (O3) for 3.75 hr/day over 5 consecutive days. Animals were given air alone 5 to 7 days before and after the 5 days of O3 exposure. The elimination half-life of theophylline ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90118-8
更新日期：1985-10-01 00:00:00
abstract：:Components of the herbicide Agent Orange--2,4-dichlorophenoxyacetic acid (2,4,-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and their esters, and the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)--and related chemicals were tested for mutagenicity using Salmonella typhimurium strains TA98, TA100, TA1535...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90084-x
更新日期：1984-08-01 00:00:00
abstract：:Studies were conducted to assess the in vitro toxicity of three chloropropanones: monochloropropanone (MCP), 1,1-dichloropropanone (1,1-DCP), and 1,3-dichloropropanone (1,3-DCP). Chloropropanones reacted directly with reduced glutathione (GSH) in sodium phosphate buffer at pH 7.4. All chloropropanones were cytotoxic t...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90192-x
更新日期：1987-10-01 00:00:00
abstract：:Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Althoug...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2017.02.003
更新日期：2017-03-15 00:00:00
abstract：:The effects of air pollution on human health are a great concern, particularly in big cities with severe traffic problems such as Bangkok, Thailand. In this study, exposure to genotoxic compounds in ambient air was studied by analysis of particle-associated polycyclic aromatic hydrocarbons (PAHs) and benzene through d...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.11.025
更新日期：2005-08-07 00:00:00
abstract：:Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2006.10.013
更新日期：2007-01-01 00:00:00
abstract：:Thiocyanate anions (SCN-) as the end products of tobacco smoke and found in the blood of cigarette smokers have been implicated in atherogenesis and heart diseases. Magnesium deficiency has also been implicated in the etiology of atherogenesis. The contractile responses of rat aorta to SCN- and the modulation of extra...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1999.8666
更新日期：1999-05-15 00:00:00
