title: ASC, a bioactive steroidal saponin from Ophitopogin japonicas, inhibits angiogenesis through interruption of Src tyrosine kinase-dependent matrix metalloproteinase pathway.
abstract: As angiogenesis is an important target for antitumour drugs, the agents that inhibit angiogenesis may help reduce the use of chemotherapy by blocking tumour blood supply. In this study, we investigated a potent angiogenesis inhibitor, ASC, a steroidal saponin compound, which has been purified from Ophitopogin japonicus (L.f) Ker.-Gawl. Our observations showed that ASC significantly suppressed human umbilical vein endothelial cell (HUVECs) growth both in vitro and in vivo. This may be resulted from the G2/M cell cycle arrest effects of ASC. Moreover, ASC inhibited HUVECs invasion and tube formation processes, which were associated with endothelial cells remodelling. A mechanism study indicated that ASC down-regulated the expression of Src tyrosine kinase, further leading to the blockage of Akt-dependent matrix metalloproteinases (mainly for MMP-9) signalling pathway, which was functionally associated with angiogenic blood vessels. Finally, ASC significantly inhibited angiogenesis and MMPs/VEGF expression in the subcutaneously injected matrigel in C57/BL mice. These findings suggest that ASC might be a potential drug candidate in anti-angiogenesis and anticancer therapies.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Ke-Wu
authors.initials: KW
authors.lastname: Zeng
authors.forename: Fang-Jiao
authors.initials: FJ
authors.lastname: Song
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Tu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D031441:Ophiopogon / Q000737:chemistry*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D012503:Saponins; D019061:src-Family Kinases; D020780:Matrix Metalloproteinase 9