title: Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions.
abstract: Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC₅₀) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant anti-metastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.
authors: College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
authors: Qin
authors: Q
authors: Zhao
authors: Zhi-dong
authors: ZD
authors: Liu
authors: Yong
authors: Y
authors: Xue
authors: Jing-feng
authors: JF
authors: Wang
authors: Hui
authors: H
authors: Li
authors: Qing-juan
authors: QJ
authors: Tang
authors: Yu-ming
authors: YM
authors: Wang
authors: Ping
authors: P
authors: Dong
authors: Chang-hu
authors: CH
authors: Xue
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects; D056945:Hep G2 Cells; D006697:Holothurin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control; D012616:Sea Cucumbers / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D006697:Holothurin; C043973:echinoside A