Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function.
Endothelial progenitor cells (EPCs) contribute to the tumor vasculature during tumor progression. Decursin isolated from the herb Angelica gigas is known to possess potent anti-inflammatory activities. Recently, we reported that decursin is a novel candidate for an angiogenesis inhibitor [Jung et al., 2009]. In this study, we investigated whether decursin regulates EPC differentiation and function to inhibit tumor vasculogenesis. We isolated AC133+ cells from human cord blood and decursin significantly decreased the number of EPC colony forming units of human cord blood-derived AC133+ cells that produce functional EPC progenies. Decursin dose-dependently decreased the cell number of EPC committing cells as demonstrated by EPC expansion studies. Decursin inhibited EPC differentiation from progenitor cells into spindle-shaped EPC colonies. Additionally, decursin inhibited proliferation and migration of early EPCs isolated from mouse bone marrow. Furthermore, decursin suppressed expression of angiopoietin-2, angiopoietin receptor Tie-2, Flk-1 (vascular endothelial growth factor receptor-2), and endothelial nitric oxide synthase in mouse BM derived EPCs in a dose-dependent manner. Decursin suppressed tube formation ability of EPCs in collaboration with HUVEC. Decursin (4 mg/kg) inhibited tumor-induced mobilization of circulating EPCs (CD34 + /VEGFR-2+ cells) from bone marrow and early incorporation of Dil-Ac-LDL-labeled or green fluorescent protein (GFP)+ EPCs into neovessels of xenograft Lewis lung carcinoma tumors in wild-type- or bone-marrow-transplanted mice. Accordingly, decursin attenuated EPC-derived endothelial cells in neovessels of Lewis lung carcinoma tumor masses grown in mice. Together, decursin likely affects EPC differentiation and function, thereby inhibiting tumor vasculogenesis in early tumorigenesis.
School of Life Sciences and Biotechnology, College of Natural Sciences, Daegu, Republic of Korea.
Seok Yun
SY
Jung
Jin Hwa
JH
Choi
Sang-Mo
SM
Kwon
Haruchika
H
Masuda
Takayuki
T
Asahara
You-Mie
YM
Lee
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D017978:Receptors, Growth Factor / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D001578:Benzopyrans; D002087:Butyrates; D016207:Cytokines; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D017978:Receptors, Growth Factor; C101278:decursin