Antiangiogenic potential of microbial metabolite elaiophylin for targeting tumor angiogenesis

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Title
Antiangiogenic potential of microbial metabolite elaiophylin for targeting tumor angiogenesis
Author(s)
H N Lim; Jun-Pil Jang; J M Han; Jae-Hyuk JangJong Seog Ahn; H J Jung
Bibliographic Citation
Molecules, vol. 23, no. 3, pp. 563-563
Publication Year
2018
Abstract
Angiogenesis plays a very important role in tumor progression through the creation of new blood vessels. Therefore, angiogenesis inhibitors could contribute to cancer treatment. Here, we show that a microbial metabolite, elaiophylin, exhibits potent antiangiogenic activity from in vitro and in vivo angiogenesis assays. Elaiophylin dramatically suppressed in vitro angiogenic characteristics such as proliferation, migration, adhesion, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by vascular endothelial growth factor (VEGF) at non-toxic concentrations. In addition, elaiophylin immensely inhibited in vivo angiogenesis of the chorioallantoic membrane (CAM) from growing chick embryos without cytotoxicity. The activation of VEGF receptor 2 (VEGFR2) in HUVECs by VEGF was inhibited by elaiophylin, resulting in the suppression of VEGF-induced activation of downstream signaling molecules, Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, nuclear factor-κB (NFκB), matrix metalloproteinase (MMP)-2 and -9 which are closely associated with VEGF-induced angiogenesis. We also found that elaiophylin blocked tumor cell-induced angiogenesis both in vitro and in vivo. Elaiophylin downregulated the expression of VEGF by inhibiting hypoxia inducible factor-1α (HIF-1α) accumulation in tumor cells. To our knowledge, these results for the first time demonstrate that elaiophylin effectively inhibits angiogenesis and thus may be utilized as a new class of natural antiangiogenic agent for cancer therapy
Keyword
angiogenesiscancer therapyelaiophylinhypoxia inducible factor-1α (HIF-1α)vascular endothelial growth factor receptor 2 (VEGFR2)
ISSN
1420-3049
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/molecules23030563
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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