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)

Although heparin can regulate angiogenesis, tumor growth and metastasis, its clinical application, as well as that of low-molecular heparin (LMWH), for treating cancer are limited because of heparin's anticoagulant activity and risk of hemorrhages. LMWH-taurocholate conjugates (LHT7), which have low anticoagulant activity, were synthesized. The structural property of LHT was evaluated by circular dichroism and the binding affinity of LHT7 to vascular endothelial growth factor 165 (VEGF(165)) was measured by isothermal titration calorimetry. The inhibitory effect of LHT7 on VEGF-mediated KDR (VEGF-receptor 2) phosphorylation in Human umbilical vein endothelial cells was evaluated. The VEGF(165) dependent Matrigel plug assay was performed to verify the antiangiogenic potential of LHT7 on a VEGF(165) inhibitor. Finally, tumor growth inhibition effects of LHT7 on SCC7 and the survival rate of animal models were investigated. Moreover, MDA-MB231 xenograft mouse model was additionally used to confirm the therapeutic effect of LHT7 on human breast cancer cell line. As a result, LHT7 which has 12.7% of anticoagulant activity of the original LMWH showed a peculiar polyproline-type helical structure. LHT7 binds to VEGF strongly and inhibits VEGF dependent KDR phosphorylation. The results of Matrigel plug assay proved LHT7 as a strong antiangiogenic agent inhibiting VEGF(165). Remarkably, LHT7 showed a significant tumor growth inhibition potential on SCC7 with an increased survival rate. LHT7 also delayed tumor growth in MDA-MB231 human breast cancer cell lines.
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PMID:Polyproline-type helical-structured low-molecular weight heparin (LMWH)-taurocholate conjugate as a new angiogenesis inhibitor. 1924 20

The aim was to study the effects and action mechanism of endostatin (ES), low molecular weight heparin-endostatin (LMWH-ES) and polyethylene glycol-endostatin (PEG-ES) on endothelial cell proliferation, choroidal neovascularization and zebrafish angiogenesis. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro. Choroidal neovascularization model was used to evaluate the effects of ES and its derivatives on choroidal neovascularization in vivo. Western blotting was employed to study the effects of ES and its derivatives on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in chorioid tissues. Zebrafish model was also used to study the anti-angiogenesis activities of ES and its derivatives. The results showed that ES and its derivatives could significantly inhibit endothelial cell proliferation in vitro (p<0.05), suppress choroidal neovascularization by down-regulating expression of VEGF and up-regulating expression of PEDF in chorioid tissues, and restrain angiogenesis in zebrafish. ES showed better activity in inhibiting endothelial cell proliferation in vitro (p<0.05), but LMWH-ES and PEG-ES showed higher activity in inhibiting choroidal neovascularization in vivo (p<0.05) and angiogenesis in zebrafish (p<0.05). These results indicate that LMWH-endostatin and PEG-endostatin are potential candidates for anti-angiogenesis drug.
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PMID:Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium derived factor make low molecular weight heparin-endostatin and polyethylene glycol-endostatin potential candidates for anti-angiogenesis drug. 2146 43