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Oncotarget. 2017 Nov 24;8(65):109217-109227. doi: 10.18632/oncotarget.22649. eCollection 2017 Dec 12.

Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo.

Lee HP1,2, Liu YC3, Chen PC4, Tai HC5,6,7, Li TM1, Fong YC8,9, Chang CS10, Wu MH11,12, Chiu LP13,14, Wang CJ15, Chen YH15, Wu YJ15, Tang CH4,16,17, Wang SW15,18.

Author information

1
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
2
Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.
3
Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan.
4
Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
5
School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
6
Department of Urology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan.
7
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
8
Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
9
Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan.
10
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
11
Physical Education Office, Tunghai University, Taichung, Taiwan.
12
Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung, Taiwan.
13
Department of Nursing, Taipei City Hospital, Taipei, Taiwan.
14
General Education Center, University of Taipei, Taipei, Taiwan.
15
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
16
Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
17
Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
18
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Accumulating evidence reports that bone marrow-derived endothelial progenitor cells (EPCs) regulate angiogenesis, postnatal neovascularization and tumor metastasis. It has been suggested that understanding the molecular targets and pharmacological functions of natural products is important for novel drug discovery. Tanshinone IIA is a major diterpene quinone compound isolated from Danshen (Salvia miltiorrhiza) and is widely used in traditional Chinese medicine (TCM). Evidence indicates that tanshinone IIA modulates angiogenic functions in human umbilical vein endothelial cells. However, the anti-angiogenic activity of tanshinone IIA in human EPCs has not been addressed. Here, we report that tanshinone IIA dramatically suppresses vascular endothelial growth factor (VEGF)-promoted migration and tube formation of human EPCs, without cytotoxic effects. We also show that tanshinone IIA markedly inhibits VEGF-induced angiogenesis in the chick embryo chorioallantoic membrane (CAM) model. Importantly, tanshinone IIA significantly attenuated microvessel formation and the expression of EPC-specific markers in the in vivo Matrigel plug assay in mice. Further, we found that tanshinone IIA inhibits EPC angiogenesis through the PLC, Akt and JNK signaling pathways. Our report is the first to reveal that tanshinone IIA reduces EPC angiogenesis both in vitro and in vivo. Tanshinone IIA is a promising natural product worthy of further development for the treatment of cancer and other angiogenesis-related pathologies.

KEYWORDS:

VEGF-A; angiogenesis; endothelial progenitor cells; tanshinone IIA

Conflict of interest statement

CONFLICTS OF INTEREST None of the authors of this paper has any financial or personal relationships with other people or organizations that could inappropriately influence this work.

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