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.