Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2

Liu, Xin, Yang, Yan, Zhang, Xiaoxiang, Xu, Shengxin, He, Shufang, Huang, Weijuan and Roberts, Michael S. (2010) Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2. Journal of Gastroenterology and Hepatology, 25 2: 420-426. doi:10.1111/j.1440-1746.2009.05981.x


Author Liu, Xin
Yang, Yan
Zhang, Xiaoxiang
Xu, Shengxin
He, Shufang
Huang, Weijuan
Roberts, Michael S.
Title Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta/Smad in HepG2
Formatted title
Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-β/Smad in HepG2 cell
Journal name Journal of Gastroenterology and Hepatology   Check publisher's open access policy
ISSN 0815-9319
1440-1746
Publication date 2010-02
Year available 2009
Sub-type Article (original research)
DOI 10.1111/j.1440-1746.2009.05981.x
Volume 25
Issue 2
Start page 420
End page 426
Total pages 7
Place of publication Carlton South, VIC, Australia
Publisher Blackwell Publishing Asia
Collection year 2011
Language eng
Subject C1
920102 Cancer and Related Disorders
060103 Cell Development, Proliferation and Death
Formatted abstract
Background and Aims:
Compound Astragalus and Salvia miltiorrhiza extract (CASE) is made up of astragalosides, astragalus polysaccharide and salvianolic acids extracted from Astragalus membranaceus Bunge (Leguminosae) and Salvia miltiorhiza Bunge (Lamiaceae) with a standard ratio. Previous reports showed that CASE inhibited hepatic fibrosis by mediating transforming growth factor (TGF)-ß/Smad signaling. This study further investigated the effect of CASE on hepatoma HepG2 cells stimulated by TGF-ß1 and its potential action mechanisms by TGF-ß/Smad signaling.

Methods:
Cell proliferation was studied by MTT assay and cell invasion was evaluated by measuring cell migration through Matrigel. Protein expression in hepatoma HepG2 cells stimulated by TGF-ß1 was analyzed by western blotting and plasminogen activator inhibitor type 1 (PAI-1) transcriptional activity in HepG2 cells was evaluated.

Results:

CASE (40 mg/mL) markedly suppressed cell invasion triggered by TGF-ß1.
Smad3 phosphorylation at the linker region (pSmad3L) and Samd2 phosphorylation at the C-terminal region (pSmad2C) were significantly reduced by CASE. Mild elevated Smad3 phosphorylation at C-terminal (pSmade3C) region was enhanced by CASE at 20 mg/mL. In addition, treatment of CASE decreased the level of Smad2/3/4 complex at 80 mg/mL, but upregulated the expression of Smad7 in a dose-dependent manner. CASE also showed inhibitory effect on PAI-1 transcriptional activity.

Conclusion:

All these results suggest that CASE exerts anti-HepG2 cell invasion effect by modulating TGF-b/Smad signaling.
Copyright © 1999–2011 John Wiley & Sons, Inc. All Rights Reserved.
Keyword Compound Astralagus and Salvia miltiorrhiza extract (CASE)
Experimental hepatocarcinogenesis
Hepatocellular carcinoma treatment
HepG2 cells
Smad
Transforming growth factor-β
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 27 Sep 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Thu, 01 Apr 2010, 12:56:49 EST by Fiona Mactaggart on behalf of Medicine - Princess Alexandra Hospital