Reference - Detail
| RRC ID | 38174 |
|---|---|
| Author | Basappa, Murugan S, Kavitha CV, Purushothaman A, Nevin KG, Sugahara K, Rangappa KS. |
| Title | A small oxazine compound as an anti-tumor agent: a novel pyranoside mimetic that binds to VEGF, HB-EGF, and TNF-α. |
| Journal | Cancer Lett |
| Abstract |
A novel pyranoside mimetic compound, DMBO (2-(2,6-difluorophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane), was designed and synthesized. The sugar mimicking behavior of DMBO was addressed by its ability to bind several growth factors/cytokines such as vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and tumor necrosis factor (TNF)-α as demonstrated by the recently developed surface plasmon resonance assay. DMBO exhibited strong anti-proliferation activity in vitro against tumor cells including a highly metastatic murine osteosarcoma cell line LM8G7 that secretes VEGF as well as two human ovarian cell lines, OVSAHO and SKOV-3, which secrete TNF-α and HB-EGF respectively. Furthermore, DMBO inhibited the metastatic activity to the mouse liver of LM8G7 cells injected from a lateral tail vein, and affected the heparan-degrading activity of LM8G7 cells. Here, we report that DMBO acts as a human heparanase inhibitor in vitro possibly as a substrate mimetic. DMBO also inhibited the migration and invasion of LM8G7 cells and angiogenic events such as endothelial cell proliferation, migration and capillary tube-like formation in vitro. More prominently, the administration of DMBO with heparin resulted in synergistic anti-tumor effects in mouse modelofosteosarcoma. These preclinical data shows the potential anti-cancer effects of DMBO. |
| Volume | 297(2) |
| Pages | 231-43 |
| Published | 2010-11-28 |
| DOI | 10.1016/j.canlet.2010.05.016 |
| PII | S0304-3835(10)00305-8 |
| PMID | 20831981 |
| MeSH | Angiogenesis Inhibitors / pharmacology Animals Benzoxazines / pharmacology* Bone Neoplasms / drug therapy Bone Neoplasms / metabolism Bone Neoplasms / pathology Cell Growth Processes / drug effects Cell Line, Tumor Cell Movement / drug effects Female Glucuronidase / antagonists & inhibitors Heparin-binding EGF-like Growth Factor Humans Intercellular Signaling Peptides and Proteins / metabolism* Liver Neoplasms, Experimental / drug therapy Liver Neoplasms, Experimental / metabolism Liver Neoplasms, Experimental / secondary Male Mice Mice, Inbred C3H Mice, Inbred C57BL Osteosarcoma / drug therapy Osteosarcoma / metabolism Osteosarcoma / pathology Ovarian Neoplasms / drug therapy Ovarian Neoplasms / metabolism Ovarian Neoplasms / pathology Protein Binding Tumor Necrosis Factor-alpha / metabolism* Vascular Endothelial Growth Factors / metabolism* |
| IF | 7.36 |
| Times Cited | 40 |
| WOS Category | ONCOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | (UV♀2(RCB1994) |