Research Papers:
Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo
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Abstract
Hsiang-Ping Lee1,2,*, Yueh-Ching Liu3,*, Po-Chun Chen4, Huai-Ching Tai5,6,7, Te-Mao Li1, Yi-Chin Fong8,9, Chih-Shiang Chang10, Min-Huan Wu11,12, Li-Pin Chiu13,14, Chia-Jung Wang15, Yi-Hsuan Chen15, Yih-Jer Wu15, Chih-Hsin Tang4,16,17 and Shih-Wei Wang15,18
1Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan
2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
3Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan
4Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
5School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
6Department of Urology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan
7Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
8Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
9Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan
10Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
11Physical Education Office, Tunghai University, Taichung, Taiwan
12Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung, Taiwan
13Department of Nursing, Taipei City Hospital, Taipei, Taiwan
14General Education Center, University of Taipei, Taipei, Taiwan
15Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
16Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
17Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
18Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
*These authors have contributed equally to this work
Correspondence to:
Shih-Wei Wang, email: [email protected]
Chih-Hsin Tang, email: [email protected]
Keywords: endothelial progenitor cells; angiogenesis; tanshinone IIA; VEGF-A
Received: July 26, 2017 Accepted: October 30, 2017 Published: November 24, 2017
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.
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