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Antiangiogenic Activity (antiangiogenic + activity)
Selected AbstractsAntitumor and Antiangiogenic Activity of Soy Phytoestrogen on 7,12-Dimethylbenz[,]anthracene-Induced Mammary Tumors Following Ovariectomy in Sprague,Dawley RatsJOURNAL OF FOOD SCIENCE, Issue 7 2009Xinmei Kang ABSTRACT:, Soy phytoestrogen is often used as hormone replacement therapy to alleviate the symptoms of menopause in postmenopausal women. Since estrogen has been considered as an important risk factor for the development of breast carcinoma, we need to know whether it is safe for these postmenopausal women with breast cancer to take soy foods that are rich in phytoestrogen. In the present study, we investigated the efficacy of soy phytoestrogen on tumor proliferation, apoptosis, and angiogenesis in mammary tumors that had already formed in ovariectomized rats. We found that soy phytochemical extraction inhibited proliferation and induced apoptosis,in vitro,and,in vivo, and it demonstrated better antitumor effects than single phytoestrogen. Soy phytochemical extraction also produced surprisingly good antiangiogenic effects, which were evidenced by lower microvascular density, reduced plasma vascular endothelial growth factor, and increased plasma endostatin levels. Our findings suggest that soy phytochemical extraction exerts significant antitumor and antiangiogenic activity in a postmenopausal animal model with breast cancer. [source] ChemInform Abstract: Modified Synthesis and Antiangiogenic Activity of Linomide.CHEMINFORM, Issue 23 2001Saeed R. Khan Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Quality control of Pulsatilla koreana based on the simultaneous determination of triterpenoidal saponins by HPLC-ELSD and principal component analysisPHYTOCHEMICAL ANALYSIS, Issue 4 2010Ki Yong Lee Abstract Introduction , Pulsatilla koreana Nakai, with triterpenoidal saponins as its main pharmacological effective compounds, is known to have several biological activities, including hypoglycaemic, antitumour, cognition-enhancing, neuroprotective, cytotoxic and antiangiogenic activities. However, few analytical methods have been reported on the quality assessment of P. koreana roots. Obejective , To establish a high-performance liquid chromatography coupled with evaporative light scattering detection for the simultaneous determination of five triterpenoidal saponins, including pulsatilloside E (1), pulsatilla saponin H (2), anemoside B4 (3), hederacolchiside E (4) and cussosaponin C (5) in P. koreana. Methodology , The chromatographic separation was performed on a Shiseido CapCell PAK C18 analytical column efficiently using gradient elution with acetonitrile and water. Results , All calibration curves showed excellent linear regressions (R2 > 0.9996) within the range of tested concentrations. The intra- and inter-day variations were below 4.78% in terms of RSD. The recoveries were 94.82,102.97% with RSD of 0.27,3.92% for spiked P. koreana samples. Conclusion , The validated method was successfully used for the analysis of five saponins in P. koreana from different locations. Moreover, the different samples were clustered in accordance with contents of triterpenoidal saponins based on aglycon type by a principal component analysis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Gallic acid is partially responsible for the antiangiogenic activities of Rubus leaf extractPHYTOTHERAPY RESEARCH, Issue 9 2006Zhijun Liu Abstract An aqueous extract of leaves from Rubus suavissimus S. Lee (Rosaceae) or sweet leaf tea was tested for antiangiogenic activity in a human tissue-based ,brin,thrombin clot angiogenesis assay. Further fractionation of this crude extract was performed and the antiangiogenic effect of individual fractions was assessed. The extract was also tested for its oral bioavailability by using the serum of normal rats gavaged with the extract in the assay. At a 0.1% w/v concentration, the extract inhibited initiation of the angiogenic response and subsequent neovessel growth from samples that had already initiated an angiogenic response. Two subfractions of the extract showed signi,cant inhibition of angiogenesis at 0.1% w/w. Gallic acid was elucidated as one of the active angiogenesis inhibitors in one fraction. A 1 mm concentration of gallic acid totally inhibited angiogenesis. In the form of leaf extract, a one-tenth concentration produced the same total inhibition as pure gallic acid. The 10-fold difference in potency suggests the presence of other active compounds contributing to the overall antiangiogenic effect of the extract. The oral absorption of this extract was tested by using serum from rats given the extract orally (gavage) in the angiogenesis assay system. The serum of rats orally administered the sweet leaf tea extract at doses of 0.1% w/w and 0.3% w/w did not signi,cantly inhibit angiogenesis. However, the serum of rats injected intraperitoneally at a dose of 0.1% w/w caused a 41% inhibition of angiogenesis compared with saline injected controls. These preliminary results warrant further bioassay directed identi,cation of other responsible compounds. Copyright © 2006 John Wiley & Sons, Ltd. [source] Pigment epithelium-derived factor binds to cell-surface F1 -ATP synthaseFEBS JOURNAL, Issue 9 2010Luigi Notari Pigment epithelium-derived factor (PEDF), a potent blocker of angiogenesis in vivo, and of endothelial cell migration and tubule formation, binds with high affinity to an as yet unknown protein on the surfaces of endothelial cells. Given that protein fingerprinting suggested a match of a , 60 kDa PEDF-binding protein in bovine retina with Bos taurus F1 -ATP synthase ,-subunit, and that F1Fo -ATP synthase components have been identified recently as cell-surface receptors, we examined the direct binding of PEDF to F1. Size-exclusion ultrafiltration assays showed that recombinant human PEDF formed a complex with recombinant yeast F1. Real-time binding as determined by surface plasmon resonance demonstrated that yeast F1 interacted specifically and reversibly with human PEDF. Kinetic evaluations revealed high binding affinity for PEDF, in agreement with PEDF affinities for endothelial cell surfaces. PEDF blocked interactions between F1 and angiostatin, another antiangiogenic factor, suggesting overlapping PEDF-binding and angiostatin-binding sites on F1. Surfaces of endothelial cells exhibited affinity for PEDF-binding proteins of , 60 kDa. Antibodies to F1,-subunit specifically captured PEDF-binding components in endothelial plasma membranes. The extracellular ATP synthesis activity of endothelial cells was examined in the presence of PEDF. PEDF significantly reduced the amount of extracellular ATP produced by endothelial cells, in agreement with direct interactions between cell-surface ATP synthase and PEDF. In addition to demonstrating that PEDF binds to cell-surface F1, these results show that PEDF is a ligand for endothelial cell-surface F1Fo -ATP synthase. They suggest that PEDF-mediated inhibition of ATP synthase may form part of the biochemical mechanisms by which PEDF exerts its antiangiogenic activity. Structured digital abstract ,,MINT-7711286: angiostatin (uniprotkb:P00747) physically interacts (MI:0915) with F-ATPase alpha subunit (uniprotkb:P07251), F-ATPase beta subunit (uniprotkb:P00830), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase delta subunit (uniprotkb:Q12165) and F-ATPase epsilon subunit (uniprotkb:P21306) by competition binding (MI:0405) ,,MINT-7711113: angiostatin (uniprotkb:P00747) physically interacts (MI:0915) with F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit(uniprotkb:P00830) and F-ATPase alpha subunit (uniprotkb:P07251) by surface plasmon resonance (MI:0107) ,,MINT-7711060: F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit (uniprotkb:P00830), F-ATPase alpha subunit (uniprotkb:P07251) and PEDF (uniprotkb:P36955) physically interact (MI:0915) by molecular sieving (MI:0071) ,,MINT-7711313: F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), PEDF (uniprotkb:P36955), F-ATPase alpha subunit (uniprotkb:P07251), F-ATPase beta subunit (uniprotkb:P00830) and F-ATPase gamma subunit(uniprotkb:P38077) physically interact (MI:0915) by molecular sieving (MI:0071) ,,MINT-7711083: PEDF (uniprotkb:P36955) physically interacts (MI:0915) with F-ATPase epsilon subunit (uniprotkb:P21306), F-ATPase delta subunit (uniprotkb:Q12165), F-ATPase gamma subunit (uniprotkb:P38077), F-ATPase beta subunit (uniprotkb:P00830) and F-ATPase alpha subunit (uniprotkb:P07251) by surface plasmon resonance (MI:0107) [source] Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Gergely P. Vasvari Abstract Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. © 2007 Wiley-Liss, Inc. [source] In vitro and in vivo antitumor effect of 2-methoxyestradiol on human melanomaINTERNATIONAL JOURNAL OF CANCER, Issue 5 2004Judit Dobos Abstract 2-methoxyestradiol (2ME2) is an endogenous metabolite of estradiol with estrogen-receptor-independent antitumor and antiangiogenic activity. We examined the effects of 2ME2 on the cellular proliferation of 8 human melanoma cell lines. We show that 2ME2 inhibited cell proliferation by inducing apoptosis and an arrest in the G2/M phase, and the mechanism of action involved microtubules, mitochondrial damage and caspase activation. In male SCID mice, 2ME2 was effective in reducing primary tumor weight and the number of liver metastases after intrasplenic injection of human melanoma cells. In the metastases, we found a significantly higher rate of apoptotic cells after 2ME2 treatment. These findings on the antitumor effect of 2ME2 in cell culture as well as in an animal model may have implications for designing alternative treatment options for patients with advanced malignant melanoma. © 2004 Wiley-Liss, Inc. [source] Antitumor and Antiangiogenic Activity of Soy Phytoestrogen on 7,12-Dimethylbenz[,]anthracene-Induced Mammary Tumors Following Ovariectomy in Sprague,Dawley RatsJOURNAL OF FOOD SCIENCE, Issue 7 2009Xinmei Kang ABSTRACT:, Soy phytoestrogen is often used as hormone replacement therapy to alleviate the symptoms of menopause in postmenopausal women. Since estrogen has been considered as an important risk factor for the development of breast carcinoma, we need to know whether it is safe for these postmenopausal women with breast cancer to take soy foods that are rich in phytoestrogen. In the present study, we investigated the efficacy of soy phytoestrogen on tumor proliferation, apoptosis, and angiogenesis in mammary tumors that had already formed in ovariectomized rats. We found that soy phytochemical extraction inhibited proliferation and induced apoptosis,in vitro,and,in vivo, and it demonstrated better antitumor effects than single phytoestrogen. Soy phytochemical extraction also produced surprisingly good antiangiogenic effects, which were evidenced by lower microvascular density, reduced plasma vascular endothelial growth factor, and increased plasma endostatin levels. Our findings suggest that soy phytochemical extraction exerts significant antitumor and antiangiogenic activity in a postmenopausal animal model with breast cancer. [source] Effect of pharmacologic plasminogen activator inhibitor-1 inhibition on cell motility and tumor angiogenesisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2006C. E. LEIK Summary.,Background:,Plasminogen activator inhibitor-1 (PAI-1) is integrally involved in tumorigenesis by impacting on both proteolytic activity and cell migration during angiogenesis. Objectives:,We hypothesized that an orally active small molecule inhibitor of PAI-1 (PAI-039; tiplaxtinin) could affect smooth muscle cell (SMC) attachment and migration in vitro on a vitronectin matrix, and exhibit antiangiogenic activity in vivo. Methods:,In vitro assays were used to assess the mechanism of inhibition of PAI-1 by PAI-039 using wild-type PAI-1 in the presence or absence of vitronectin and wild-type PAI-1 and specific PAI-1 mutants in SMC adhesion and migration assays. An in vivo tumor angiogenesis model was used to assess the effect of PAI-039 administration on neovascularization in a Matrigel implant. Results:,PAI-039 dose-dependently inhibited soluble, but not vitronectin-bound, PAI-1. Cell adhesion assays using PAI-1 mutants unable to bind vitronectin (PAI-1K) or inactivate proteases (PAI-1R) further suggested that PAI-039 inactivated PAI-1 by binding near its vitronectin domain. In a tumor angiogenesis model, PAI-039 treatment of wild-type mice dose-dependently decreased hemoglobin concentration and endothelial cell staining within the Matrigel implant, indicating reduced angiogenesis, but exhibited no in vivo efficacy in PAI-1 null mice. Conclusions:,Administration of an orally active PAI-1 inhibitor prevented angiogenesis in a Matrigel implant. The lack of activity of PAI-039 against wild-type PAI-1 bound to vitronectin and PAI-1K suggests PAI-039 binding near the vitronectin-binding site. Our studies further substantiate a role for PAI-1 in cellular motility and tumor angiogenesis, and suggest for the first time that these effects can be modulated pharmacologically. [source] Gallic acid is partially responsible for the antiangiogenic activities of Rubus leaf extractPHYTOTHERAPY RESEARCH, Issue 9 2006Zhijun Liu Abstract An aqueous extract of leaves from Rubus suavissimus S. Lee (Rosaceae) or sweet leaf tea was tested for antiangiogenic activity in a human tissue-based ,brin,thrombin clot angiogenesis assay. Further fractionation of this crude extract was performed and the antiangiogenic effect of individual fractions was assessed. The extract was also tested for its oral bioavailability by using the serum of normal rats gavaged with the extract in the assay. At a 0.1% w/v concentration, the extract inhibited initiation of the angiogenic response and subsequent neovessel growth from samples that had already initiated an angiogenic response. Two subfractions of the extract showed signi,cant inhibition of angiogenesis at 0.1% w/w. Gallic acid was elucidated as one of the active angiogenesis inhibitors in one fraction. A 1 mm concentration of gallic acid totally inhibited angiogenesis. In the form of leaf extract, a one-tenth concentration produced the same total inhibition as pure gallic acid. The 10-fold difference in potency suggests the presence of other active compounds contributing to the overall antiangiogenic effect of the extract. The oral absorption of this extract was tested by using serum from rats given the extract orally (gavage) in the angiogenesis assay system. The serum of rats orally administered the sweet leaf tea extract at doses of 0.1% w/w and 0.3% w/w did not signi,cantly inhibit angiogenesis. However, the serum of rats injected intraperitoneally at a dose of 0.1% w/w caused a 41% inhibition of angiogenesis compared with saline injected controls. These preliminary results warrant further bioassay directed identi,cation of other responsible compounds. Copyright © 2006 John Wiley & Sons, Ltd. [source] Chemical synthesis and biotinylation of the thrombospondin domain TSR2PROTEIN SCIENCE, Issue 5 2009Theresa K. Tiefenbrunn Abstract The type 1 repeat domain from thrombospondin has potent antiangiogenic activity and a structurally interesting fold, making it an attractive target for protein engineering. Chemical synthesis is an attractive approach for studying protein domains because it enables the use of unnatural amino acids for site-specific labeling and detailed structure-function analysis. Here, we demonstrate the first total chemical synthesis of the thrombospondin type 1 repeat domain by native chemical ligation. In addition to the natural domain, five sites for side chain modification were evaluated and two were found to be compatible with oxidative folding. Several challenges were encountered during peptide synthesis due to the functional complexity of the domain. These challenges were overcome by the use of new solid supports, scavengers, and the testing of multiple ligation sites. We also describe an unusual sequence-specific protecting group migration observed during cleavage resulting in +90 Da and +194 Da adducts. Synthetic access to this domain enables the synthesis of a number of variants that can be used to further our understanding of the biochemical interaction network of thrombospondin and provide insight into the structure and function of this important antitumorogenic protein domain. [source] Antiangiogenic plasma activity in patients with systemic sclerosisARTHRITIS & RHEUMATISM, Issue 10 2007Mary Jo Mulligan-Kehoe Objective Systemic sclerosis (SSc; scleroderma) is a systemic connective tissue disease with an extensive vascular component that includes aberrant microvasculature and impaired wound healing. The aim of this study was to investigate the presence of antiangiogenic factors in patients with SSc. Methods Plasma samples were obtained from 30 patients with SSc and from 10 control patients without SSc. The samples were analyzed for the ability of plasma to affect endothelial cell migration and vascular structure formation and for the presence of antiangiogenic activity. Results Exposure of normal human microvascular dermal endothelial cells to plasma from patients with SSc resulted in decreased cell migration (mean ± SEM 52 ± 5%) and tube formation (34 ± 6%) compared with that in plasma from control patients (P < 0.001 for both). SSc plasma contained 2.9-fold more plasminogen kringle 1,3 fragments (angiostatin) than that in control plasma. The addition of angiostatin to control plasma resulted in inhibition of endothelial cell migration and proliferation similar to that observed in SSc plasma. In vitro studies demonstrated that granzyme B and other proteases contained in T cell granule content cleave plasminogen and plasmin into angiostatin fragments. Conclusion Plasminogen conformation in patients with SSc enables granzyme B and granule content protease to limit the proangiogenic effects of plasmin and increase the levels of antiangiogenic angiostatin. This increase in angiostatin production may account for some of the vascular defects observed in patients with SSc. [source] A phase 1 trial of 2 dose schedules of ABT-510, an antiangiogenic, thrombospondin-1-mimetic peptide, in patients with advanced cancer,CANCER, Issue 12 2008Michael S. Gordon MD Abstract BACKGROUND. ABT-510 is a substituted nonapeptide that mimics the antiangiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). The current study was designed to establish the safety of ABT-510 in the treatment of patients with advanced malignancies on a once-daily (QD) and twice-daily dosing schedule. METHODS. Patients were randomly assigned to 1 of 6 dosing regimens: 20 mg, 50mg, or 100 mg QD or 10 mg, 25 mg, or 50 mg twice daily. ABT-510 was administered by subcutaneous bolus injection in cycles of 28 days. Tumor response and disease progression were monitored at 8-week intervals by computed tomography scan or magnetic resonance imaging. RESULTS. Thirty-six patients were randomly assigned in equal numbers to the 6 study regimens, with an additional 13 patients randomized to the 10-mg-twice-daily and 50-mg-twice-daily ABT-510 regimens. The expected pharmacokinetic target was achieved at all dose levels tested. The majority of adverse events were grade 1 or 2 (according to National Cancer Institute Common Toxicity Criteria [version 2]) and were not found to be dose related. The most frequently reported adverse events that were possibly related to ABT-510 included injection site reactions, asthenia, headache, and nausea. Grade 3 events considered to possibly be related included nausea, dyspnea, bone pain, constipation, vomiting, asthenia, and chills and tremors. One partial response was observed in a patient with carcinosarcoma who received 20 mg QD. The 6-month progression-free survival rate was 6%. Approximately 42% of patients (21 of 50 patients) had stable disease for ,3 months. CONCLUSIONS. ABT-510 can be administered at doses of 20 mg/day to 100 mg/day without significant toxicity. In the current study, minimal antitumor activity was observed, which was similar to observations in other single-agent antiangiogenic trials. Cancer 2008. © 2008 American Cancer Society. [source] Hierarchical Mechanochemical Switches in AngiostatinCHEMBIOCHEM, Issue 11 2006Fabio Grandi Abstract We wish to propose a novel mechanism by which the triggering of a biochemical signal can be controlled by the hierarchical coupling between a protein redox equilibrium and an external mechanical force. We have characterized this mechanochemical mechanism in angiostatin, and we have evidence that it can switch the access to partially unfolded structures of this protein. We have identified a metastable intermediate that is specifically accessible under thioredoxin-rich reducing conditions, like those met by angiostatin on the surface of a tumor cell. The structure of the same intermediate accounts for the unexplained antiangiogenic activity of angiostatin. These findings demonstrate a new link between redox biology and mechanically regulated processes. [source] | |||||||||||||