Antiangiogenic potentials of ahpatinins obtained from a Streptomyces species

Cited 0 time in scopus
Metadata Downloads
Title
Antiangiogenic potentials of ahpatinins obtained from a Streptomyces species
Author(s)
Jang Mi Han; Jun-Pil JangJae-Hyuk JangJong Seog Ahn; H J Jung
Bibliographic Citation
Oncology Reports, vol. 43, no. 2, pp. 625-634
Publication Year
2020
Abstract
While exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil-derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated. In the present study, the antiangiogenic properties of ahpatinins C, E and G were investigated. The results revealed that the natural compounds significantly inhibited the vascular endothelial growth factor (VEGF)-induced proliferation, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs) without exhibiting any cytotoxicity. It was also revealed that ahpatinin E effectively suppressed the neovascularization of the chorioallantoic membranes in growing chick embryos. Notably, ahpatinins C, E, and G led to the downregulation of VEGF-induced activation of VEGF receptor 2 (VEGFR2) and its downstream signaling mediators, including AKT, ERK1/2, JNK, p38, and NF-κB, in HUVECs. Moreover, they reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the HUVECs following stimulation with VEGF. Furthermore, ahpatinins C, E, and G reduced the tumor cell?induced invasion and tube forming abilities of HUVECs, as well as the expression of VEGF, by suppressing hypoxia-inducible factor-1α (HIF-1α) activity in U87MG glioblastoma cells. Collectively, the present findings indicated that ahpatinins C, E, and G may be used in anticancer therapy by targeting tumor angiogenesis through the inhibition of both VEGFR2 and HIF-1α pathways.
Keyword
AhpatininsHIF-1αStreptomyces spTumor angiogenesisVEGFR2
ISSN
1021-335X
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/or.2019.7446
Type
Article
Appears in Collections:
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.