Two cyclic hexapeptides from Penicillium sp. FN070315 with antiangiogenic activities

Jun Pil Jang, Hye Jin Jung, Jang Mi Han, Narae Jung, Yonghyo Kim, Ho Jeong Kwon, Sung Kyun Ko, Nak Kyun Soung, Jae Hyuk Jang, Jong Seog Ahn

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Abstract

In the course of searching for angiogenesis inhibitors from microorganisms, two cyclic peptides, PF1171A (1) and PF1171C (2) were isolated from the soil fungus Penicillium sp. FN070315. In the present study, we investigated the antiangiogenic efficacy and associated mechanisms of 1 and 2 in vitro using human umbilical vein endothelial cells (HUVECs). Compounds 1 and 2 inhibited the proliferation of HUVECs at concentrations not exhibiting cytotoxicity. Moreover, 1 and 2 significantly suppressed vascular endothelial growth factor (VEGF)-induced migration, invasion, proliferation and tube formation of HUVECs as well as neovascularization of the chorioallantoic membrane in developing chick embryos. We also identified an association between the antiangiogenic activity of 1 and 2 and the downregulation of both the phosphorylation of VEGF receptor 2 and the expression of hypoxia inducible factor-1α at the protein level. Taken together, these results further suggest that compounds 1 and 2 will be promising angiogenesis inhibitors.

Original languageEnglish
Article numbere0184339
JournalPloS one
Volume12
Issue number9
DOIs
Publication statusPublished - 2017 Sep

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Jang, J. P., Jung, H. J., Han, J. M., Jung, N., Kim, Y., Kwon, H. J., Ko, S. K., Soung, N. K., Jang, J. H., & Ahn, J. S. (2017). Two cyclic hexapeptides from Penicillium sp. FN070315 with antiangiogenic activities. PloS one, 12(9), [e0184339]. https://doi.org/10.1371/journal.pone.0184339