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KIST/PU Nanostructured Heparin Derivatives as an Angiogenesis Inhibitor

By Youngro Byun

College of Pharmacy, Seoul National University, Seoul, Korea

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Abstract

Although low molecular weight heparin (LMWH) has been known to regulate angiogenesis, tumor growth and metastasis, the administration of heparin for treating cancer is limited in clinical application due to its unsatisfactory therapeutic effects and a strong anticoagulant activity, which induces hemorrhages. LMWH-Taurocholate conjugate (HT10), which has low anticoagulant activity as well as a number of sulfations was prepared. Circular dichroism method was used to evaluate a structural property of heparin derivatives. Lactate dehydrogenase (LDH) test was carried out in order to evaluate cytotoxic effects of HT10 on human umbilical vein endothelial cells (HUVECs) and squamous cell carcinoma cells (SCC7). Vascular endothelial growth factor 165 (VEGF165) dependent Matrigel plug assay and bFGF dependent HUVECs tubular formation test were performed to verify the antiangiogenic potential of HT10 as an VEGF165 and bFGF inhibitor. Finally tumor growth inhibition effects of HT10 were investigated in SCC7 and MDA-MB231 xenograft mouse models. Apart from other heparin derivatives, HT10 which has 12.7% of anticoagulant activity showed peculiar polyproline–helical structure. The results of HUVECs tubular formation and Matrigel plug assay bolstered the action of HT10 as an antiangiogenic agent inhibiting VEGF165 as well as bFGF functions. In tumor growth inhibition experiments, HT10 showed a significant tumor growth inhibition potential on SCC7; moreover it delayed a development of MDA-MB231 effectively. Polyproline-helical structured HT10 showed significant antiangiogenic potential and tumor growth inhibitory effect.

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Researchers should cite this work as follows:

  • Youngro Byun (2011), "KIST/PU Nanostructured Heparin Derivatives as an Angiogenesis Inhibitor," https://nanohub.org/resources/12651.

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Burton Morgan 121, Purdue University, West Lafayette, IN

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