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

International Journal of Molecular Sciences

Yi-Ling Ma¹  Ming-Hong Tai¹  Chang-Yi Wu¹  Chung-Lung Cho¹  Youn-Shen Bee²  Ming-Chi Chang³  Hua-Chang Fang⁴  Kang-Ju Chou⁴  Wen-Tsan Weng⁵  Tian-Huei Chu⁶  Shih-Wei Lin⁷ 

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

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

DOI  :  10.3390/ijms150916611

来源: DOAJ

【 摘 要 】

Angiogenesis, the process of neovascularization, plays an important rolein 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】

Unknown