A Novel Poly-Naphthol Compound ST104P Suppresses Angiogenesis by Attenuating Matrix Metalloproteinase-2 Expression in Endothelial Cells

International Journal of Molecular Sciences

Yi-Ling Ma⁴  Shih-Wei Lin³  Hua-Chang Fang⁶  Kang-Ju Chou⁶  Youn-Shen Bee⁷  Tian-Huei Chu⁵  Ming-Chi Chang¹  Wen-Tsan Weng²  Chang-Yi Wu⁴  Chung-Lung Cho⁴ 

[1] Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; E-Mail:;Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan; E-Mail:;National Sun Yat-sen University and Academia Sinica Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; E-Mail:;Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; E-Mails:;Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan; E-Mail:;Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; E-Mails:;Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 804, Taiwan; E-Mail:

关键词: ST104P;    angiogenesis;    Lewis lung carcinoma;    matrix metalloproteinase-2 (MMP-2);   

DOI  :  10.3390/ijms150916611

来源: mdpi

【 摘 要 】

Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels’ development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs). Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.