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Title 

Antiangiogenic potential of microbial metabolite elaiophylin for targeting tumor angiogenesis

Authors 

H N LimJun-Pil JangJ M HanJae-Hyuk JangJong Seog AhnH J Jung

Publisher 

MDPI

Issue Date 

2018

Citation 

Molecules

Keywords 

angiogenesiscancer therapyelaiophylinhypoxia inducible factor-1α (HIF-1α)vascular endothelial growth factor receptor 2 (VEGFR2)

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

ISSN 

1420-3049

Link 

http://dx.doi.org/10.3390/molecules23030563

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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