title: Chemical Conjugate of Low Molecular Weight Heparin and Suramin Fragment Inhibits Tumor Growth Possibly by Blocking VEGF165.
abstract: Low molecular weight heparin (LMWH) and its derivatives have been reported to possess antiangiogenic effect via electrostatic interaction with various angiogenic growth factors such as VEGF165. However, clinical applications of LMWH for anticancer therapy have been restricted due to its anticoagulant effect and insufficient therapeutic efficacy. To overcome these limitations and enhance the antiangiogenic efficacy, LMWH was conjugated with suramin fragments that have a binding affinity to the heparin-binding domain (HBD) of proteins. The conjugation of suramin fragments to LMWH enhanced the antiangiogenic effect of LMWH by increasing the binding affinity to VEGF165, while decreasing its anticoagulant activity. The chemical conjugate of LMWH and suramin fragments (LHsura) showed a substantial inhibitory effect on VEGF165-mediated cell proliferation, migration, and tube formation of HUVECs without significant cytotoxicity in vitro. Finally, we confirmed the anticancer effect of LHsura (61.4% vs control) in a SCC7-bearing mouse model.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Jooho
authors.initials: J
authors.lastname: Park
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Ji-young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chosun University , 309 Pilmun-daero, Dong-gu, Gwangju 501-759, South Korea.
authors.forename: Seung Rim
authors.initials: SR
authors.lastname: Hwang
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Foyez
authors.initials: F
authors.lastname: Mahmud
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 151-742, South Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul 151-742, South Korea.
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D013498:Suramin / Q000008:administration & dosage / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D006495:Heparin, Low-Molecular-Weight; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013498:Suramin
keywords: VEGF165; angiogenesis inhibitor; chemical conjugate; low molecular weight heparin; suramin