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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

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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 antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.

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Authors and Affiliations

  1. College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China

    Qin Zhao, Zhi-dong Liu, Yong Xue, Jing-feng Wang, Hui Li, Qing-juan Tang, Yu-ming Wang, Ping Dong & Chang-hu Xue

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  1. Qin Zhao
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  2. Zhi-dong Liu
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  3. Yong Xue
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  4. Jing-feng Wang
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  5. Hui Li
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  6. Qing-juan Tang
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  7. Yu-ming Wang
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  8. Ping Dong
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  9. Chang-hu Xue
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Corresponding authors

Correspondence to Jing-feng Wang or Chang-hu Xue.

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Project supported by the National High-Tech R & D Program (863) of China (No. 2007AA091805), and the National Natural Science Foundation of China (Nos. 30972284 and 30871944)

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Zhao, Q., Liu, Zd., Xue, Y. et al. 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. J. Zhejiang Univ. Sci. B 12, 534–544 (2011). https://doi.org/10.1631/jzus.B1000217

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  • DOI: https://doi.org/10.1631/jzus.B1000217

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