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

被引:10
作者
Ma, Yi-Ling [1 ,2 ]
Lin, Shih-Wei [3 ,4 ]
Fang, Hua-Chang [2 ]
Chou, Kang-Ju [2 ]
Bee, Youn-Shen [5 ]
Chu, Tian-Huei [6 ]
Chang, Ming-Chi [7 ]
Weng, Wen-Tsan [8 ]
Wu, Chang-Yi [1 ]
Cho, Chung-Lung [1 ]
Tai, Ming-Hong [1 ,3 ,4 ,6 ,9 ]
机构
[1] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 804, Taiwan
[2] Kaohsiung Vet Gen Hosp, Div Nephrol, Kaohsiung 813, Taiwan
[3] Natl Sun Yat Sen Univ, Kaohsiung 804, Taiwan
[4] Natl Sun Yat Sen Univ, Acad Sinica, Doctoral Degree Program Marine Biotechnol, Kaohsiung 804, Taiwan
[5] Kaohsiung Vet Gen Hosp, Dept Ophthalmol, Kaohsiung 804, Taiwan
[6] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 804, Taiwan
[7] Kaohsiung Vet Gen Hosp, Div Colorectal Surg, Kaohsiung 813, Taiwan
[8] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 701, Taiwan
[9] Kaohsiung Med Univ, Ctr Stem Cell Res, Kaohsiung 807, Taiwan
关键词
ST104P; angiogenesis; Lewis lung carcinoma; matrix metalloproteinase-2 (MMP-2); GROWTH; CANCER; INHIBITORS; MIGRATION; MMP-9; WATER; NEOVASCULARIZATION; COMPLEXATIONS; MECHANISMS; ENDOSTATIN;
D O I
10.3390/ijms150916611
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
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.
引用
收藏
页码:16611 / 16627
页数:17
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