論文 - 詳細
| RRC ID | 18635 |
|---|---|
| 著者 | Watari K, Nakamura M, Fukunaga Y, Furuno A, Shibata T, Kawahara A, Hosoi F, Kuwano T, Kuwano M, Ono M. |
| タイトル | The antitumor effect of a novel angiogenesis inhibitor (an octahydronaphthalene derivative) targeting both VEGF receptor and NF-κB pathway. |
| ジャーナル | Int J Cancer |
| Abstract |
Development of a novel type of angiogenesis inhibitor will be essential for further improvement of therapeutics against cancer patients. We examined whether an octahydronaphthalene derivative, AMF-26, which was screened as an inhibitor of intercellular adhesion molecule-1 (ICAM-1) production stimulated by inflammatory stimuli in vascular endothelial cells, could block angiogenesis in response to vascular endothelial growth factor (VEGF) and/or inflammatory cytokines. Low dose AMF-26 effectively inhibited the tumor necrosis factor-α (TNF-α)- or the interleukin-1β (IL-1β)-induced production of ICAM-1 in human umbilical vascular endothelial cells (HUVECs). We found that the TNF-α-induced phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear translocation of p65 were impaired by AMF-26 in both endothelial cells and cancer cells. AMF-26 was found to inhibit the phosphorylation of VEGF receptor 1 (VEGFR1), VEGFR2 and the downstream signaling molecules Akt, extracellular signal-regulated kinase (ERK)1/2 stimulated by VEGF in HUVECs. Therefore, the VEGF-induced proliferation, migration and tube formation of vascular endothelial cells was highly susceptible to inhibition by AMF-26. Oral administration of AMF-26 significantly blocked VEGF- or IL-1β-induced angiogenesis in the mouse cornea, and also tumor angiogenesis and growth. Together, our results indicate that AMF-26 inhibits angiogenesis through suppression of both VEGFR1/2 and nuclear factor-κB (NF-κB) signaling pathways when stimulated by VEGF or inflammatory cytokines. AMF-26 could be a promising novel candidate drug for cancer treatments. |
| 巻・号 | 131(2) |
| ページ | 310-21 |
| 公開日 | 2012-7-15 |
| DOI | 10.1002/ijc.26356 |
| PMID | 21826646 |
| MeSH | Angiogenesis Inhibitors / pharmacology* Animals Cell Line Cell Movement Cell Proliferation Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / metabolism Human Umbilical Vein Endothelial Cells Humans I-kappa B Proteins / metabolism Intercellular Adhesion Molecule-1 / biosynthesis Interleukin-1beta / antagonists & inhibitors Male Mice Mice, Inbred BALB C Mice, Inbred C57BL NF-KappaB Inhibitor alpha NF-kappa B / metabolism* Naphthols / pharmacology* Neovascularization, Physiologic / drug effects* Neovascularization, Physiologic / physiology Oncogene Protein v-akt / metabolism Phosphorylation Pyridines / pharmacology* Receptors, Vascular Endothelial Growth Factor / metabolism* Signal Transduction / drug effects Transcription Factor RelA / antagonists & inhibitors Tumor Necrosis Factor-alpha / antagonists & inhibitors |
| IF | 5.145 |
| 引用数 | 14 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16/BL6(RCB2638) |