Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function

被引:24
作者
Jung, Seok Yun [2 ,3 ]
Choi, Jin Hwa [2 ]
Kwon, Sang-Mo [3 ]
Masuda, Haruchika [4 ]
Asahara, Takayuki [4 ]
Lee, You-Mie [1 ,2 ,5 ]
机构
[1] Kyungpook Natl Univ, Vasc Network Res Lab, Coll Pharm, Taegu 702701, South Korea
[2] Coll Nat Sci, Sch Life Sci & Biotechnol, Taegu, South Korea
[3] Pusan Natl Univ, Sch Med, Dept Physiol, Pusan 609735, South Korea
[4] Tokai Univ, Sch Med, Dept Regenerat Med Sci, Tokai, Ibaraki 2591193, Japan
[5] Kyungpook Natl Univ, Pharmaceut Sci Res Inst, Taegu 702701, South Korea
关键词
DECURSIN; ENDOTHELIAL PROGENITOR CELL; SDF-1a; TUMOR MICROVESSELS; VEGF-INDUCED ANGIOGENESIS; NITRIC-OXIDE SYNTHASE; BONE-MARROW; ANGELICA GIGAS; GENE-THERAPY; NEOVASCULARIZATION; MOBILIZATION; ACTIVATION; PROTEIN; KINASE;
D O I
10.1002/jcb.24085
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (4mg/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. J. Cell. Biochem. 113: 14781487, 2012. (C) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:1478 / 1487
页数:10
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