In:
Molecular Carcinogenesis, Wiley, Vol. 50, No. 12 ( 2011-12), p. 945-960
Abstract:
β‐escin, a triterpene saponin, is one of the major active compounds extracted from horse chestnut ( Aesculus hippocastanum ) seed. Previous work has found that β‐escin sodium has antiinflammatory and antitumor effects. In the present study, we investigated its effect on cell proliferation and inducible nitric‐oxide synthase (iNOS) expression in human lung carcinoma A549 cells. β‐escin sodium (5–40 µg/mL) inhibited cytokine mixture (CM)‐induced nitric oxide (NO) production in A549 cells by reducing the expression of iNOS. β‐escin sodium suppressed phosphorylation and nuclear translocation of STAT1 (Tyr701) and STAT3 (Tyr705) induced by CM but did not affect the activation of c‐Jun and NF‐κB. β‐escin sodium inhibited the activation of protein tyrosine kinase JAK2. Pervanadate treatment reversed the β‐escin sodium‐induced downregulation of STAT3 and STAT1. β‐escin sodium treatment enhanced an activating phosphorylation of the phosphatase SHP2. Small interfering RNA‐mediated knockdown of SHP2 inhibited β‐escin sodium‐induced phospho‐STAT dephosphorylation. Moreover β‐escin sodium reduced the activation of p38 MAPK. Finally, β‐escin sodium inhibited the proliferation of A549 cells, did not change the cell membrane's permeability, nuclear morphology and size and the mitochondria's transmembrane potential of A549 cells. Taken together, these results demonstrate that β‐escin sodium could downregulate iNOS expression through inhibiting JAK/STAT signaling and p38 MAPK activation in A549 cells. β‐escin sodium has a marked antiproliferative effect on A549 cells at least in part by inhibiting the JAK/STAT signaling pathway, but not by a cytotoxic effect. β‐escin sodium would be useful as a chemopreventive agent or a therapeutic against inflammatory‐associated tumor. © 2011 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0899-1987
,
1098-2744
Language:
English
Publisher:
Wiley
Publication Date:
2011
detail.hit.zdb_id:
2001984-1
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