title: A novel poly-naphthol compound ST104P suppresses angiogenesis by attenuating matrix metalloproteinase-2 expression in endothelial cells.
abstract: 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.
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. ylma@vghks.gov.tw.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Ma
authors.affiliation: National Sun Yat-sen University and Academia Sinica Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. shiwey0214@gmail.com.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. hcfang@vghks.gov.tw.
authors.forename: Hua-Chang
authors.initials: HC
authors.lastname: Fang
authors.affiliation: Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. kjchou@vghks.gov.tw.
authors.forename: Kang-Ju
authors.initials: KJ
authors.lastname: Chou
authors.affiliation: Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 804, Taiwan. ysbee@vghks.gov.tw.
authors.forename: Youn-Shen
authors.initials: YS
authors.lastname: Bee
authors.affiliation: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. skbboyz0817@gmail.com.
authors.forename: Tian-Huei
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan. mcchang@vghks.gov.tw.
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan. bpvincent@gmail.com.
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Weng
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. cywu@mail.nsysu.edu.tw.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. clcho@mail.nsysu.edu.tw.
authors.forename: Chung-Lung
authors.initials: CL
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan. minghongtai@gmail.com.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects; D009282:Naphthalenesulfonates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015027:Zebrafish / Q000196:embryology
chemical_list: D020533:Angiogenesis Inhibitors; D047028:Macrocyclic Compounds; D009282:Naphthalenesulfonates; C000598177:ST104P compound; D020778:Matrix Metalloproteinase 2