Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genistein has been reported to be a natural chemopreventive in several types of human cancer. In our prior study, soy isoflavones were shown to induce cell cycle arrest and apoptosis of bladder cancer cells in the range of human urine excretion. This study was designed to identify the novel molecular basis underlying anti-angiogenic activities of soy isoflavones. An immortalized E6 and five human bladder cancer cell lines were studied by immunoassay, flow cytometry, functional activity, reverse transcription-polymerase chain reaction, immunoblotting, and transwell co-culture in vitro. The efficacy of soy isoflavones on angiogenesis inhibition in vivo was examined by nude mice xenograft and chick chorioallantoic membrane bioassay. Factors analyzed included angiogenic factors, matrix-degrading enzymes, and angiogenesis inhibitors. Genistein was the most potent inhibitor of angiogenesis in vitro and in vivo among the isoflavone compounds tested. It may also account for most of the reduced microvessel density of xenografts observed and the suppressed endothelial migration by soy isoflavones. Genistein exhibited a dose-dependent inhibition of expression/excretion of vascular endothelial growth factor165, platelet-derived growth factor, tissue factor, urokinase plasminogen activator, and matrix metalloprotease-2 and 9, respectively. On the other hand, there was an up-regulation of angiogenesis inhibitors-plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1. In addition, a differential inhibitory effect between immortalized uroepithelial cells and most cancer cell lines was also observed. Altogether, we discovered that tissue factor, endostatin, and angiostatin are novel molecular targets of genistein. The current investigation provides further evidence in support of soy-based foods as natural dietary inhibitors of tumor angiogenesis.
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PMID:The novel targets for anti-angiogenesis of genistein on human cancer cells. 1562 83

Angiogenesis plays a critical role in the pathogenesis of malignant tumor growth and metastases. Since cyclooxygenase (COX)-2 expression is positively correlated with vascular endothelial growth factor (VEGF) expression and enhanced angiogenesis, COX-2 inhibitors have been focused on as angiogenesis-inhibiting drugs that may offer a complementary modality to classical strategies for cancer therapy. In this study, we evaluated the potential antiangiogenic effects of 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3), a dual COX/5-LOX inhibitor. In HT1080 cancer cells, FPP-3 significantly suppressed release of VEGF as well as activation of NF-kappaB, a transcriptional factor required for VEGF expression. In a chick chorioallantoic membrane (CAM) assay, FPP-3 dose-dependently suppressed VEGF- and MCF-7 human breast cancer cell-induced angiogenesis. In experiments with human umbilical vein endothelial cells (HUVECs), FPP-3 dose-dependently decreased not only the cell survival and proliferation but also the tube formation and invasion using Matrigel-coated plates. Such antiangiogenic activity correlated with suppression of VEGF-induced matrix metalloproteinase (MMP)-2 expression, reactive oxygen species (ROS) production, and extracellularly regulated kinase (ERK) phosphorylation. Furthermore, in contrast to the case of NS398, a selective COX-2 inhibitor, FPP-3 did not alter the ratio of tissue factor (TF)/tissue factor pathway inhibitor (TFPI) expression, a coagulation index. These results indicate that FPP-3 could be used as an effective antiangiogenic agent without the risk of developing thrombotic complications.
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PMID:The anti-angiogenic effects of 1-furan-2-yl-3-pyridin-2-yl-propenone are mediated through the suppression of both VEGF production and VEGF-induced signaling. 1906 39

Cancer-related venous thromboembolism (VTE) is frequent and constitutes the second leading cause of death in patients with cancer. High platelet count is one of independent predictive factors of cancer-associated VTE. Besides the implication of platelets in cancer-associated VTE, recent clinical and experimental evidences support that platelets play several roles in the progression of malignancies and inversely, cancer can also influence platelet count and activity. The objective of this report is to review the current literature regarding the role of platelets in cancer through experimental results and population-based studies. Platelets are implicated in cancer progression and metastasis through proangiogenic factors (growth factors and signaling pathways), antiangiogenic factors (angiostatin, endostatin, thrombospondin-1), and matrix metalloproteinases. In addition, platelets are involved in cancer-associated thrombosis and thus tumor cell-induced platelet activation, through anionic phospholipids on their surface, released soluble factors, such as P-selectin, CD40 ligand, platelet factor 4, thrombospondin-1 or beta-thromboglobulin, tumor cell procoagulant proteins (tissue factor, urokinase-type plasminogen activator, plasminogen activator inhibitor type 1), and microparticles. Due to these different mechanisms, platelets may represent a potential therapeutic target. The main current treatments against platelets are: (1) acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs, nonselective cyclo-oxygenase (COX)-1 and COX-2 inhibitors, which are associated with decreased cancer incidence and better overall survival and (2) irreversible inhibitor of P2Y12 subtype which decreases cancer incidence. Platelets are key players in tumor growth, metastasis, and cancer-associated thrombosis. This multifaceted role identifies them as a relevant therapeutic target for prevention of cancer occurrence and treatment of cancer.
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PMID:Involvement of Platelets in Cancers. 3138 5