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Antiproliferative Properties (antiproliferative + property)
Selected AbstractsDevelopment of Sulfonamide Compounds as Potent Methionine Aminopeptidase Type II Inhibitors with Antiproliferative Properties.CHEMINFORM, Issue 44 2006Megumi Kawai Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] A Sugar-Modified Phosphole Gold Complex with Antiproliferative Properties Acting as a Thioredoxin Reductase Inhibitor in MCF-7 CellsCHEMMEDCHEM, Issue 11 2008Elodie Viry A phosphine-coordinated gold(I) thiosugar complex was found to exert potent cytotoxic and antiproliferative effects through thioredoxin reductase inhibition in MCF-7 cells. [source] Antiproliferative properties of polyketides isolated from Virola sebifera leavesPHYTOTHERAPY RESEARCH, Issue 1 2008Carina Denny Abstract An activity-guided fractionation of Virola sebifera Aubl. methylene chloride-soluble fraction provided novel 3,5-dihydro-2-(1,-oxo-3,-hexadecenyl)-2-cyclohexen-1-one (3), two known lignans (1, 2) and dehydro hexadecanoyl resorcinol (4). Isolation and purification were conducted with the application of column chromatography and structures were assigned by spetral analysis (1D and 2D NMR, HREIMS). Compounds 1,4 were evaluated for cytotoxic activities against human tumour cell lines UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal) and NCI-ADR (breast expressing phenotype multiple drugs resistance) in vitro. The new polyketide (3) showed selectivity against human OVCAR03 and NCI-ADR cell lines, ranging from 2 to 4 µg/mL. Copyright © 2007 John Wiley & Sons, Ltd. [source] [Tris(pyrazolyl)methane]ruthenium Complexes Capable of Inhibiting Cancer Cell GrowthEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 31 2009Jesse M. Walker Abstract The [tris(pyrazolyl)methane]ruthenium complexes [(,3 -tpm)RuCl(solv)2]PF6 [tpm = tris(pyrazolyl)methane; solv = MeCN, dmso] and [(,3 -tpm)RuCl(LL)]PF6 [LL = ,2 -dppe, ,2 -dppp, ,2 -dppb, (PMePh2)2] have been prepared, characterized and screened in vitro for their antiproliferative properties against the MCF-7 (breast) and HeLa (cervical) cancer cell lines by using the MTT assay. Although the MeCN and dmso complexes showed no activity under the conditions used, the phosphane complexes exhibited remarkable cytotoxic behaviour. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Loco-regional treatment of hepatocellular carcinoma,HEPATOLOGY, Issue 2 2010Riccardo Lencioni Loco-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded. Radiofrequency ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation,including microwave ablation, irreversible electroporation, and light-activated drug therapy,seem to have potential to overcome the limitations of radiofrequency ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic, noninvasive multinodular tumors at the intermediate stage. The recent introduction of embolic microspheres that have the ability to release the drug in a controlled and sustained fashion has been shown to significantly increase safety and efficacy of TACE with respect to conventional, lipiodol-based regimens. The available data for radioembolization with yttrium-90 suggests that this is a potential new option for patients with HCC, which should be investigated in the setting of randomized controlled trials. Despite the advances and refinements in loco-regional approaches, the long-term survival outcomes of patients managed with interventional techniques are not fully satisfactory, mainly because of the high rates of tumor recurrence. The recent addition of molecular targeted drugs with antiangiogenic and antiproliferative properties to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between loco-regional and systemic treatments. The outcomes of these trials are eagerly awaited, because they have the potential to revolutionize the treatment of HCC. (HEPATOLOGY 2010;) [source] Gold compounds as anticancer agents: chemistry, cellular pharmacology, and preclinical studiesMEDICINAL RESEARCH REVIEWS, Issue 3 2010Stefania Nobili Abstract Gold compounds are a class of metallodrugs with great potential for cancer treatment. During the last two decades, a large variety of gold(I) and gold(III) compounds are reported to possess relevant antiproliferative properties in vitro against selected human tumor cell lines, qualifying themselves as excellent candidates for further pharmacological evaluation. The unique chemical properties of the gold center confer very interesting and innovative pharmacological profiles to gold-based metallodrugs. The primary goal of this review is to define the state of the art of preclinical studies on anticancer gold compounds, carried out either in vitro or in vivo. The available investigations of anticancer gold compounds are analyzed in detail, and particular attention is devoted to underlying molecular mechanisms. Notably, a few biophysical studies reveal that the interactions of cytotoxic gold compounds with DNA are generally far weaker than those of platinum drugs, implying the occurrence of a substantially different mode of action. A variety of alternative mechanisms were thus proposed, of which those involving either direct mitochondrial damage or proteasome inhibition or modulation of specific kinases are now highly credited. The overall perspectives on the development of gold compounds as effective anticancer drugs with an innovative mechanism of action are critically discussed on the basis of the available experimental evidence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 3, 550,580, 2010 [source] Flavonoids as RTK inhibitors and potential anticancer agentsMEDICINAL RESEARCH REVIEWS, Issue 5 2008Florence Teillet Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715,745, 2008 [source] In Vitro culture studies of FlorEssence® on human tumor cell linesPHYTOTHERAPY RESEARCH, Issue 2 2005Joseph Tai Abstract FlorEssence® (FE) is an herbal tea widely used by patients to treat chronic conditions in North America, particularly cancer patients during chemo- and radiation therapy. Although individual components of FE have antioxidant, antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of anticancer activity for the herbal tea itself is still lacking. We studied the antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the proliferation of both breast and leukemia cells in vitro only at high concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20 dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells, with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells showed a significantly increased Sub G0[sol ]G1 fraction after treatment with 1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7 and MDA-MB-468 breast cancer cells were treated with a combination of FE with either paclitaxel or cisplatin, results showed that only the combination of 1[sol ]20 dilution of FE with 0.5 µM cisplatin resulted in a small but significantly higher MCF7 cell survival than 0.5 µM cisplatin treatment alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the antiproliferative properties of these two commonly used chemotherapeutic agents. The results suggest that FE at high concentrations show differential inhibitory effect on different human cancer cell lines. Further studies are needed to assess the biological activities of FE. Copyright © 2005 John Wiley & Sons, Ltd. [source] Differential expression of peroxisome proliferator activated receptor , and cyclin D1 does not affect proliferation of asthma- and non-asthma-derived airway smooth muscle cellsRESPIROLOGY, Issue 2 2010Justine Y. LAU ABSTRACT Background and objective: Airway remodelling involves thickening of the airway smooth muscle (ASM) bulk. Proliferation of asthma-derived ASM cells is increased in vitro, but underlying mechanisms remain unknown. Peroxisome proliferators activated receptor-, (PPAR,) regulates the cell cycle. It is suggested that PPAR, agonists have anti-inflammatory effects, which may be valuable in the treatment of asthma, but information regarding their antiproliferative properties in ASM is lacking. Although corticosteroids reduce airway inflammation, in vitro they inhibit proliferation in only non-asthma ASM cells by reducing cyclin D1. We therefore investigated the effects of mitogenic stimulation (foetal bovine serum (FBS)), and a PPAR, ligand (ciglitazone), on PPAR, and cyclin D1 expression and proliferation of ASM cells. In addition, we examined the effects of ciglitazone on ASM cell proliferation. Methods: We assessed PPAR, and cyclin D1 mRNA and protein levels using quantitative PCR and immunoblotting. Cell proliferation was assessed using bromodeoxyuridine uptake. Results: In the presence of 5% FBS, PPAR, and cyclin D1 expression decreased over time in non-asthmatic cells but increased in asthmatic cells (compared with sub-confluent cells). FBS-induced proliferation of asthmatic cells increased at all time points, but occurred only at day 7 with non-asthmatic cells (compared with unstimulated time-matched control). Ciglitazone increased PPAR, expression in both groups, but did not alter cell proliferation, while fluticasone increased PPAR, protein only in asthmatic cells. Conclusions: Although in the presence of a mitogenic stimulus, PPAR, was differentially expressed in asthma- and non-asthma-derived ASM; its expression was not related to the increased proliferation observed in asthmatic ASM. [source] Parallel Synthesis of O -Phenoxyethyl and O -Adamantyl N- acyl Thiocarbamates Endowed with Antiproliferative ActivityARCHIV DER PHARMAZIE, Issue 6 2009Andrea Spallarossa Abstract In order to further explore the antiproliferative properties of O -phenoxyethyl and O -adamantyl acylthiocarbamates (ATCs), a series of 14 derivatives was prepared by a parallel adaptation of a highly convergent one-pot three-step procedure. Ten acylthiocarbamates were selected by the National Cancer Institute drug evaluation program and screened against a panel of 55 to 58 cell lines derived from nine different types of human cancers. In general, the tested compounds showed a widespread micromolar activity with some specificity against leukemia, renal UO-31, central nervous system (CNS) SNB-75, and non-small cell lung HOP-92 cancer cell lines. Bioinformatic COMPARE analyses were carried out to identify possible mechanism(s) of action for acylthiocarbamate antiproliferative activity. [source] The novel ruthenium,, -linolenic complex [Ru2(aGLA)4Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential, increased reactive oxygen species generation and apoptosis in vitroCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2010Geise Ribeiro Abstract The present study reports the synthesis of a novel compound with the formula [Ru2(aGLA)4Cl] according to elemental analyses data, referred to as Ru2GLA. The electronic spectra of Ru2GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru2GLA was synthesized with the aim of combining and possibly improving the anti-tumour properties of the two active components ruthenium and , -linolenic acid (GLA). The properties of Ru2GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru2GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru2GLA enters the cells and ICP-AES elemental analysis found an increase in ruthenium from <0.02 to 425,mg/Kg in treated cells. The sub-G1 apoptotic cell population was increased by Ru2GLA (22,±,5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru2GLA (44,±,2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18,±,1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru2GLA exposed cells. The EC50 for Ru2GLA decreased with increasing time of exposure from 285,µM at 24,h, 211,µM at 48,h to 81,µM at 72,h. In conclusion, Ru2GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright © 2009 John Wiley & Sons, Ltd. [source] The Ether Lipid Inositol-C2-PAF is a Potent Inhibitor of Cell Proliferation in HaCaT CellsCHEMBIOCHEM, Issue 3 2006Annette Fischer Abstract The search for specific anticancer drugs that do not interfere with DNA synthesis or influence the cytoskeleton has led to the development of modified phospholipids with antiproliferative properties. These compounds cause remodeling of the structure and function of plasma membranes. Recently, we described novel compounds, the glycosidated phospholipids, that surprisingly inhibit cell proliferation. These compounds contain ,- D -glucose in the sn -2 position of the glycerol backbone of phosphatidylcholine (PC) and platelet-activating factor (PAF), which gives rise to 2-glucophosphatidylcholine (Glc-PC) and 1- O -octadecyl-2- O -,- d- glucopyranosyl- sn -2-glycero-3-phosphatidylcholine (Glc-PAF), respectively. Glc-PC and Glc-PAF inhibit the growth of HaCaT cells at nontoxic concentrations. Here we report the introduction of myo -inositol, in place of ,- D -glucose, in the sn -2 position of the glycerol backbone; this leads to two diastereomeric 1- O -octadecyl-2- O -(2-(myo -inositolyl)-ethyl)- sn -glycero-3-(R/S)-phosphatidylcholines (Ino-C2-PAF). The inositol-containing PAF enhances the antiproliferative capacity (IC50=1.8 ,M) and reduces the cytotoxicity relative to Glc-PAF (LC50=15 ,M). Through biological assays, we showed that, in HaCaT cells, Ino-C2-PAF causes upregulation of the keratinocyte-specific differentiation marker involucrin, increases the activity of the differentiation marker transglutaminase, and induces apoptosis at nontoxic concentrations. Ino-C2-PAF therefore seems to be a promising candidate for development as an antiproliferative drug for the treatment of hyperproliferative diseases of the skin. [source] Heparin Coating of Small-Caliber Decellularized Xenografts Reduces Macrophage Infiltration and Intimal HyperplasiaARTIFICIAL ORGANS, Issue 6 2009Wei-Wei Cai Abstract Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 ± 0.12 vs. 0.345 ± 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts. [source] | |||||||||||||