A natural anti-inflammatory enone fatty acid inhibits angiogenesis by attenuating nuclear factor-κB signaling in vascular endothelial cells

Ayana Furuno, Kosuke Watari, Nakamura Mamiyo, Fukunaga Yuichi, Jee H. Jung, Mayumi Ono

研究成果: Contribution to journalArticle査読

6 被引用数 (Scopus)

抄録

An anti-inflammatory enone fatty acid, (E)-9-oxooctadec-10-enoic acid (C10), was previously isolated from red alga (Gracilaria verrucosa). Of the many cellular signaling pathways activated in response to the inflammatory stimulus, lipopolysaccharide, the extracellular signalregulated kinase 1/2, the stress-activated protein kinase/Jun N-terminal kinase and the nuclear factor-κB pathways were specifically blocked by C10 in the macrophage-like cell line, RAW264.7. In this study, we investigated the anti-angiogenic and anti-inflammatory activities of C10 in endothelial cells. C10 only partially inhibited the proliferation of human cancer cell lines at relatively high concentrations of over 20 μg/ml. However, C10 inhibited the proliferation of RAW264.7 cells and human umbilical vein endothelial cells (HUVECs) with half-maximal inhibitory concentration (IC50) values of 4-8 μg/ml. Both the proliferation and the migration of HUVECs induced by the vascular endothelial growth factor (VEGF) were markedly blocked by C10 with IC 50 values of 2-3 μg/ml. The activation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α, by tumor necrosis factor-α or VEGF in these cells was also blocked by C10. Furthermore, in an in vivo model of angiogenesis in the mouse cornea, the neovascularization induced by VEGF was markedly inhibited by C10. The processes involved in inflammatory signaling, angiogenesis, and the development of malignancy in cancer are closely related, suggesting that C10 could be a useful lead compound for the development of novel anti-angiogenic therapies for cancer.

本文言語英語
ページ(範囲)493-501
ページ数9
ジャーナルInternational journal of oncology
38
2
DOI
出版ステータス出版済み - 2 2011

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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