Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway

Abstract

Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms. Here, we show the antiangiogenic effects of decursin and decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases. Taken together, these results demonstrate that decursin and decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.

Runx2 Protein Stabilizes Hypoxia-inducible Factor-1α through Competition with von Hippel-Lindau Protein (pVHL) and Stimulates Angiogenesis in Growth Plate Hypertrophic Chondrocytes

“…Cell Proliferation Assay-Proliferation of HUVECs was assayed as described previously (33). CM was used after starvation with low serum medium (1% FBS in M199).…”

“…Cell Migration Assay-Migration was measured using 24-well transwell units with polycarbonate filters with an 8-m pore size (Costar, Lowell, MA), as described previously (33). The lower compartment contained 600 l of CM, and 5 ϫ 10 4 cells were resuspended in 100 l of DMEM and placed in the upper part of a transwell plate.…”

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway

“…7,8 Decursinol angelate (DA) is an active pyranocoumarin compound, isolated from the roots of Angelica gigas Nakai (Umbelliferae), that exhibits chemo-preventive and anti-inflammatory activities. 9 DA has been reported to suppress the growth of estrogen-stimulated and estrogen-independent growth and survival of breast cancer MCF-7 and MDA-MB-231 cells. 10 DA also suppresses the growth of cancer cells through the inhibition of phosphatidylinositol 3 0 -kinase (PI3K)/Akt, extracellular-signal-regulated kinase (Erk) and nuclear factor-kB (NFkB).…”

“…11 Additionally, DA has anti-angiogenic activity both in vitro and in vivo. 9 DA has been demonstrated to have antileukemic activity through the suppression of protein kinase C activation in human leukemia cells; however, the mechanism underlying this action requires investigation. 12 Furthermore, it has been hypothesized that the anti-inflammatory activity of DA will contribute to its potential effects on cancer cells.…”

Improvement in antiproliferative activity of Angelica gigas Nakai by solid dispersion formation via hot-melt extrusion and induction of cell cycle arrest and apoptosis in HeLa cells

“…6) The major active components of AGN are coumarins (decursin and decursinol angelate). 7) They are also known to have several biological activities, such as anticancer activity, 8) anti-amnestic activity, 9) and anti-allergic effect. 10) Decursin and decursinol angelate are the main hydrophobic phytochemical components of the root of AGN.…”