Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α.

Abstract

Antiangiogenesis is now thought of as one of the most important approaches for anticancer therapy. In this study, we determined the antiangiogenic property of herboxidiene, a polyketide natural product. Herboxidiene effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) at concentrations not exhibiting cytotoxicity. Furthermore, the natural product significantly suppressed vascular endothelial growth factor-induced invasion and tube formation in HUVECs as well as neovascularization of the chorioallantoic membrane in developing chick embryos. We also identified an association between the antiangiogenic activity of herboxidiene and the downregulation of both the phosphorylation of VEGF receptor 2 (KDR/Flk-1) and the expression of hypoxia-inducible factor-1α at the transcriptional level. These results suggest that herboxidiene functions as a potential antiangiogenic agent and may be applicable for anticancer therapy by targeting tumor angiogenesis.

• Authors: Hye Jin Jung, Yonghyo Kim, Ju Yong Shin, Jae Kyung Sohng, Ho Jeong Kwon
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 38 Issue 9 Pg. 1728-35 (Sep 2015) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 26195285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Fatty Alcohols
• Hypoxia-Inducible Factor 1, alpha Subunit
• Pyrans
• herboxidiene
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Chick Embryo
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects, physiology)
• Fatty Alcohols (pharmacology)
• Hep G2 Cells
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Pyrans (pharmacology)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, metabolism)